Molecular Cancer最新文献

{"title":"Radioresistance in rectal cancer: can nanoparticles turn the tide?","authors":"Diogo Coelho, Diogo Estêvão, Maria José Oliveira, Bruno Sarmento","doi":"10.1186/s12943-025-02232-x","DOIUrl":"https://doi.org/10.1186/s12943-025-02232-x","url":null,"abstract":"Rectal cancer accounts for over 35% of the worldwide colorectal cancer burden representing a distinctive subset of cancers from those arising in the colon. Colorectal cancers exhibit a continuum of traits that differ with their location in the large intestine. Due to anatomical and molecular differences, rectal cancer is treated differently from colon cancer, with neoadjuvant chemoradiotherapy playing a pivotal role in the control of the locally advanced disease. However, radioresistance remains a major obstacle often correlated with poor prognosis. Multifunctional nanomedicines offer a promising approach to improve radiotherapy response rates, as well as to increase the intratumoral concentration of chemotherapeutic agents, such as 5-Fluorouracil. Here, we revise the main molecular differences between rectal and colon tumors, exploring the complex orchestration beyond rectal cancer radioresistance and the most promising nanomedicines reported in the literature to improve neoadjuvant therapy response rates. ","PeriodicalId":19000,"journal":{"name":"Molecular Cancer","volume":"4 1","pages":""},"PeriodicalIF":37.3,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143056476","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sorafenib enhanced the function of myeloid-derived suppressor cells in hepatocellular carcinoma by facilitating PPARα-mediated fatty acid oxidation","authors":"Chunxiao Li, Liting Xiong, Yuhan Yang, Ping Jiang, Junjie Wang, Mengyuan Li, Shuhua Wei, Suqing Tian, Yuexuan Wang, Mi Zhang, Jie Tang","doi":"10.1186/s12943-025-02238-5","DOIUrl":"https://doi.org/10.1186/s12943-025-02238-5","url":null,"abstract":"Sorafenib, an FDA-approved drug for advanced hepatocellular carcinoma (HCC), faces resistance issues, partly due to myeloid-derived suppressor cells (MDSCs) that enhance immunosuppression in the tumor microenvironment (TME). Various murine HCC cell lines and MDSCs were used in a series of in vitro and in vivo experiments. These included subcutaneous tumor models, cell viability assays, flow cytometry, immunohistochemistry, and RNA sequencing. MDSCs were analyzed for chemotaxis, immunosuppressive functions, fatty acid oxidation (FAO), and PPARα expression. The impact of sorafenib on tumor growth, MDSC infiltration, differentiation, and immunosuppressive function was assessed, alongside the modulation of these processes by PPARα. Here, we revealed increased infiltration and enhanced function of MDSCs in TME after treatment with sorafenib. Moreover, our results indicated that sorafenib induced the accumulation of MDSCs mediated by CCR2, and pharmacological blockade of CCR2 markedly reduced MDSCs migration and tumor growth. Mechanistically, sorafenib promoted the effect and fatty acid uptake ability of MDSCs and modulated peroxisome proliferator-activated receptor α (PPARα)-mediated fatty acid oxidation (FAO). In addition, tumor-bearing mice fed a high-fat diet (HFD) at the beginning of sorafenib administration had worse outcomes than mice fed a regular diet. Genetic deficiency of PPARα weakens the effect of sorafenib on MDSCs in mice with HCC. Pharmacological inhibition of PPARα has a synergistic anti-tumor effect with sorafenib, which is attenuated by the inhibition of MDSCs. Mechanistically, sorafenib significantly inhibited the differentiation of macrophages by upregulating PPARα expression and suppressing the PU.1-CSF1R pathway. Overall, our study demonstrated that sorafenib enhanced the function of MDSCs by facilitating PPARα-mediated FAO and further augmenting sorafenib resistance, which sheds light on dietary management and improves the therapeutic response in HCC.","PeriodicalId":19000,"journal":{"name":"Molecular Cancer","volume":"45 1","pages":""},"PeriodicalIF":37.3,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143050033","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: LncRNA LINRIS stabilizes IGF2BP2 and promotes the aerobic glycolysis in colorectal cancer","authors":"Yun Wang, Jia-Huan Lu, Qi-Nian Wu, Ying Jin, De-Shen Wang, Yan-Xing Chen, Jia Liu, Xiao-Jing Luo, Qi Meng, Heng-Ying Pu, Ying-Nan Wang, Pei-Shan Hu, Ze-Xian Liu, Zhao-Lei Zeng, Qi Zhao, Rong Deng, Xiao-Feng Zhu, Huai-Qiang Ju, Rui-Hua Xu","doi":"10.1186/s12943-025-02229-6","DOIUrl":"https://doi.org/10.1186/s12943-025-02229-6","url":null,"abstract":"<p><b>Correction</b><b>: </b><b>Mol Cancer 18, 174 (2019)</b></p><p><b>https://doi.org/10.1186/s12943-019-1105-0</b></p><br/><p>The authors identified two errors happened inadvertently in Figure 7 and Figure S5 after a self-investigation and carefully check of the original [1] published version.</p><p>The authors apologize for the error in Figure 7B. The annotations on the top of the last graph were wrongly typed. The annotations shall be “LDHA-low” and “LDHA-high”. The correct figure is shown below.</p><figure><picture><source srcset=\"//media.springernature.com/lw685/springer-static/image/art%3A10.1186%2Fs12943-025-02229-6/MediaObjects/12943_2025_2229_Figa_HTML.png?as=webp\" type=\"image/webp\"/><img alt=\"figure a\" aria-describedby=\"Figa\" height=\"187\" loading=\"lazy\" src=\"//media.springernature.com/lw685/springer-static/image/art%3A10.1186%2Fs12943-025-02229-6/MediaObjects/12943_2025_2229_Figa_HTML.png\" width=\"685\"/></picture></figure><p><b>Figure 7. Illustration of LINRIS-IGF2BP2-MYC axis in CRC. (B)</b> Percentages of specimens showing different levels of Ki-67, IGF2BP2, MYC, GLUT-1 and PKM2 and LDHA in the low or high LINRIS expression groups (n = 220, Chi-square test, **P < 0.01)</p><p>The authors also apologize for the error in Figure S5E. The ki-67 image of Ctrl was mistakenly uploaded. The correct figure is shown below.</p><figure><picture><source srcset=\"//media.springernature.com/lw685/springer-static/image/art%3A10.1186%2Fs12943-025-02229-6/MediaObjects/12943_2025_2229_Figb_HTML.png?as=webp\" type=\"image/webp\"/><img alt=\"figure b\" aria-describedby=\"Figb\" height=\"511\" loading=\"lazy\" src=\"//media.springernature.com/lw685/springer-static/image/art%3A10.1186%2Fs12943-025-02229-6/MediaObjects/12943_2025_2229_Figb_HTML.png\" width=\"685\"/></picture></figure><p><b>Figure S5. In vivo experiments elucidated the effect of the inhibition of LINRIS in CRC. (E)</b> Representative images of H&E staining, immunohistochemistry staining of Ki-67 and TUNEL from the tumor sections. Scale bar, 100 μm</p><ol data-track-component=\"outbound reference\" data-track-context=\"references section\"><li data-counter=\"1.\"><p>Wang Y, Lu JH, Wu QN, et al. LncRNA <i>LINRIS</i> stabilizes IGF2BP2 and promotes the aerobic glycolysis in colorectal cancer. Mol Cancer. 2019;18:174. https://doi.org/10.1186/s12943-019-1105-0.</p><p>Article PubMed PubMed Central CAS Google Scholar </p></li></ol><p>Download references<svg aria-hidden=\"true\" focusable=\"false\" height=\"16\" role=\"img\" width=\"16\"><use xlink:href=\"#icon-eds-i-download-medium\" xmlns:xlink=\"http://www.w3.org/1999/xlink\"></use></svg></p><span>Author notes</span><ol><li><p>Yun Wang, Jia-Huan Lu, Qi-Nian Wu and Ying Jin contributed equally to this work.</p></li></ol><h3>Authors and Affiliations</h3><ol><li><p>State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, China</p><p>Yun Wang, Jia-Huan Lu, Qi-Nian Wu, Ying Jin, De-Shen Wa","PeriodicalId":19000,"journal":{"name":"Molecular Cancer","volume":"4 1","pages":""},"PeriodicalIF":37.3,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143044065","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CircTTC13 promotes sorafenib resistance in hepatocellular carcinoma through the inhibition of ferroptosis by targeting the miR-513a-5p/SLC7A11 axis","authors":"Ying Zhang, Ruiwei Yao, Mingyi Li, Chongkai Fang, Kunliang Feng, Xiuru Chen, Jinan Wang, Rui Luo, Hanqian Shi, Xinqiu Chen, Xilin Zhao, Hanlin Huang, Shuwei Liu, Bing Yin, Chong Zhong","doi":"10.1186/s12943-024-02224-3","DOIUrl":"https://doi.org/10.1186/s12943-024-02224-3","url":null,"abstract":"The high mortality rate from hepatocellular carcinoma (HCC) is due primarily to challenges in early diagnosis and the development of drug resistance in advanced stages. Many first-line chemotherapeutic drugs induce ferroptosis, a form of programmed cell death dependent on ferrous iron-mediated oxidative stress, suggesting that drug resistance and ensuing tumor progression may in part stem from reduced ferroptosis. Since circular RNAs (circRNAs) have been shown to influence tumor development, we examined whether specific circRNAs may regulate drug-induced ferroptosis in HCC. Through circRNA sequencing, we identified a novel hsa_circ_0000195 (circTTC13) that is overexpressed in HCC tissues. This overexpression is linked to higher tumor grade, more advanced tumor stage, decreased ferroptosis, and poorer overall survival. Overexpression of CircTTC13 in HCC cell lines and explant tumors was associated with increased proliferation rates, enhanced metastatic capacity, and resistance to sorafenib, while also inhibiting ferroptosis. Conversely, circTTC13 silencing reduced malignant characteristics and promoted ferroptosis. In silico analysis, luciferase assays, and fluorescence in situ hybridization collectively demonstrated that circTTC13 directly targets and reduces miR-513a-5p expression, which in turn leads to the upregulation of the negative ferroptosis regulator SLC7A11. Moreover, the inhibition of SLC7A11 mirrored the effect of circTTC13 knockdown, whereas ferroptosis inhibition mimicked the effect of circTTC13 overexpression. Both circTTC13 and SLC7A11 were highly expressed in drug-resistant HCC cells, and circTTC13 silencing induced ferroptosis and reversed sorafenib resistance in explant tumors. These findings identify circTTC13 as a critical driver of HCC progression and resistance to drug-induced ferroptosis via upregulation of SLC7A11. The cicTTC13/miR-513a-5p/SLC7A11 axis represents a potential therapeutic target for HCC.","PeriodicalId":19000,"journal":{"name":"Molecular Cancer","volume":"84 1","pages":""},"PeriodicalIF":37.3,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143044103","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: Intra-tumoral sphingobacterium multivorum promotes triple-negative breast cancer progression by suppressing tumor immunosurveillance","authors":"Zhikai Mai, Liwu Fu, Jiyan Su, Kenneth K.W. To, Chuansheng Yang, Chenglai Xia","doi":"10.1186/s12943-025-02237-6","DOIUrl":"https://doi.org/10.1186/s12943-025-02237-6","url":null,"abstract":"<p><b>Correction: Mol Cancer 24</b>,<b> 6 (2025)</b></p><p><b>https://doi.org/10.1186/s12943-024-02202-9</b></p><p>Following the publication of the original article [1], the authors would like to update the texts under the Fig. 4 caption or legend.</p><p> The texts under the Fig. 4 caption currently reads:</p><p> Propionylcarnitine which was decreased by <i>S. multivorum</i> inhibits tumor growth <i>in vivo.</i> (<b>A</b>) Heatmap showing potential biomarker levels in mouse tumors. The screening criteria were <i>p</i> < 0.05 and |log2FC| ≥ 0 for unidimensional analysis, and VIP value > 1 for multidimensional analysis. (<b>B</b>) Pathway enrichment analysis of differential metabolites using pathway-associated metabolite sets (SMPDB). (<b>C</b>) Volcano plot showing the differential metabolites based on one-dimensional statistical screening. Differential metabolites were considered significant at a threshold of <i>p</i> < 0.05 and |log2FC| ≥ 0. (<b>D-F</b>) Concentration of short-chain acylcarnitine metabolites in mouse tumors. (<b>G</b>) The effect of propionylcarnitine on cell viability of MDA-MB-231, BT20, and 4T1 cell lines in vitro. (<b>H</b>) The effect of propionylcarnitine on spleen lymphocyte viability in BALB/c mice. (<b>I</b>) The number of Treg cells in splenic lymphocytes of BALB/c mice by flow cytometry analysis. (<b>L</b>) Images of representative 4T1 subcutaneous tumors after the intra-tumoral injection of the <i>S. multivorum</i> in BALB/c mice. PBS served as a negative control. 2 × 10<sup>7</sup> CFU of <i>S. multivorum</i> were injected into subcutaneous tumors as described above. 150 mg/kg propionylcarnitine was injected into the tumor twice a week. After 26 days, the subcutaneous tumors were isolated and shown. (<b>M</b>) Tumor growth curve in BALB/c mice. (<b>N</b>) Tumor weight in BALB/c mice. (<b>O</b>) Body weight of BALB/c mice. Statistical significance was determined by an unpaired two-tailed Student’s t-test for (<b>D-F</b>) and ANOVA statistical test with a Tukey’s post-hoc analysis for (<b>H</b>-<b>K</b>, <b>N</b>). Significance levels are denoted as *<i>p</i> < 0.05; **<i>p</i> < 0.01; ***<i>p</i> < 0.001.</p><p> The texts under the Fig. 4 caption should read:</p><p> Propionylcarnitine which was decreased by S. multivorum inhibits tumor growth in vivo. (<b>A</b>) Heatmap showing potential biomarker levels in mouse tumors. The screening criteria were <i>p</i> < 0.05 and |log2FC| ≥ 0 for unidimensional analysis, and VIP value > 1 for multidimensional analysis. (<b>B</b>) Pathway enrichment analysis of differential metabolites using pathway-associated metabolite sets (SMPDB). (<b>C</b>) Volcano plot showing the differential metabolites based on one-dimensional statistical screening. Differential metabolites were considered significant at a threshold of <i>p</i> < 0.05 and |log2FC| ≥ 0. (<b>D-F</b>) Concentration of short-chain acylcarnitine metabolites in mouse tumors. (<b>G</b>) The effect of ","PeriodicalId":19000,"journal":{"name":"Molecular Cancer","volume":"113 1","pages":""},"PeriodicalIF":37.3,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143044101","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The micro(nano)plastics perspective: exploring cancer development and therapy","authors":"Xiangying Deng, Yajun Gui, Lin Zhao","doi":"10.1186/s12943-025-02230-z","DOIUrl":"https://doi.org/10.1186/s12943-025-02230-z","url":null,"abstract":"Microplastics, as an emerging environmental pollutant, have received widespread attention for their potential impact on ecosystems and human health. Microplastics are defined as plastic particles less than 5 millimeters in diameter and can be categorized as primary and secondary microplastics. Primary microplastics usually originate directly from industrial production, while secondary microplastics are formed by the degradation of larger plastic items. Microplastics are capable of triggering cytotoxicity and chronic inflammation, and may promote cancer through mechanisms such as pro-inflammatory responses, oxidative stress and endocrine disruption. In addition, improved microplastics bring new perspectives to cancer therapy, and studies of microplastics as drug carriers are underway, showing potential for high targeting and bioavailability. Although current studies suggest an association between microplastics and certain cancers (e.g., lung, liver, and breast cancers), the long-term effects and specific mechanisms still need to be studied. This review aimed at exploring the carcinogenicity of microplastics and their promising applications in cancer therapy provides important directions for future research and emphasizes the need for multidisciplinary collaboration to address this global health challenge.","PeriodicalId":19000,"journal":{"name":"Molecular Cancer","volume":"67 1","pages":""},"PeriodicalIF":37.3,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143027198","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Circular RNA circBNC2 inhibits tumorigenesis by modulating ferroptosis and acts as a nanotherapeutic target in prostate cancer","authors":"Xiang Pan, Kailai Chen, Wei Gao, Meiqi Xu, Fanlong Meng, Mengyuan Wu, Zi Qi Wang, Yun Qi Li, Wanhai Xu, Manjie Zhang, Yakun Luo","doi":"10.1186/s12943-025-02234-9","DOIUrl":"https://doi.org/10.1186/s12943-025-02234-9","url":null,"abstract":"Metastasis is a leading cause of cancer-related death in castration-resistant prostate cancer (CRPC) patients. Circular RNAs (circRNAs) have emerged as key regulators of the metastasis of various cancers. However, the functional effects and regulatory mechanisms of circRNAs in metastatic CRPC (mCRPC) remain largely unknown. The expression of circBNC2 in prostate cancer (PCa), CRPC and neuroendocrine prostate cancer (NEPC) tissues was analyzed through bioinformatics analysis. Functional assays, including cell proliferation, migration, invasion and ferroptosis, were conducted in vitro and in vivo. The interactions between circBNC2, miR-4298, and ACSL6 were explored via luciferase reporter assays, RNA immunoprecipitation, and western blotting analysis. In addition, for the first time in PCa, we developed novel nanobowls (NBs) loaded with docetaxel (DTX) and circBNC2 (Dc-NBs) and evaluated the antitumor efficacy of Dc-NBs in a photothermal therapy (PTT) strategy. We identified a novel tumor-suppressive circRNA, circBNC2, in human PCa, CRPC and NEPC samples via bioinformatic analysis. CircBNC2 expression was significantly downregulated in PCa tissues and PCa cell lines. Functional assays demonstrated that circBNC2 inhibited PCa cell proliferation and migration both in vitro and in vivo. Mechanistically, circBNC2 acted as a sponge for miR-4298, and ACSL6 was identified as a direct target of the circBNC2/miR-4298 axis. Moreover, we demonstrated that ACSL6 is essential for mediating circBNC2-regulated ferroptosis in PCa cells. More importantly, we demonstrated the nanodelivery of Dc-NBs, which exhibited significant antitumor effects in both subcutaneous and metastatic PCa models. This study revealed the tumor-suppressive role of circBNC2 in mCRPC by driving ferroptosis via the circBNC2/miR-4298/ACSL6 axis. Additionally, we developed an efficient and safe PTT strategy based on a nanodelivery system that codelivers circBNC2 and DTX, highlighting its potential as a novel therapeutic approach for mCRPC.","PeriodicalId":19000,"journal":{"name":"Molecular Cancer","volume":"13 1","pages":""},"PeriodicalIF":37.3,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143027221","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comprehensive single-cell atlas of colorectal neuroendocrine tumors with liver metastases: unraveling tumor microenvironment heterogeneity between primary lesions and metastases","authors":"Yiqiao Deng, Qichen Chen, Chengyao Guo, Jinghua Chen, Xin Li, Zhiyu Li, Yefan Zhang, Jianjun Zhao, Jianguo Zhou, Jianqiang Cai, Tao Yan, Xiaobing Wang, Xinyu Bi, Zhen Huang, Hong Zhao","doi":"10.1186/s12943-025-02231-y","DOIUrl":"https://doi.org/10.1186/s12943-025-02231-y","url":null,"abstract":"Colorectal neuroendocrine tumors with liver metastases (CRNELM) are associated with a poorer prognosis compared to their nonmetastatic counterparts. A comprehensive understanding of the tumor microenvironment (TME) heterogeneity between primary lesions (PL) and liver metastases (LM) could provide crucial insights for enhancing clinical management strategies for these patients. We utilized single-cell RNA sequencing to analyze fresh tissue samples from CRNELM patients, aiming to elucidate the variations in TME between PL and LM. Complementary multidimensional validation was achieved through spatial transcriptomics, bulk RNA sequencing, and multiplex immunohistochemistry/immunofluorescence. Our single-cell RNA sequencing analysis revealed that LM harboured a higher proportion of CD8 + T cells, CD4 + T cells, NK cells, NKT cells, and B cells exhibiting a stress-like phenotype compared to PL. RGS5 + pericytes may play a role in the stress-like phenotype observed in immune cells within LM. MCs in PL (PL_MCs) and LM (LM_MCs) exhibit distinct activation of tumor-associated signaling pathways. Notably, COLEC11 + matrix cancer-associated fibroblasts (COLEC11_mCAFs) were found to be significantly associated with LM_MCs. Cell communication analysis unveiled potential targetable receptor-ligand interactions between COLEC11_mCAFs and LM_MCs. Multidimensional validation confirmed the prominence of the characteristic stress-like phenotypes, including HSPA6_CD8_Tstr, HSPA6_NK, and COLEC11_mCAFs in LM. Moreover, a higher abundance of COLEC11_mCAFs correlated with poorer survival rates in the neuroendocrine tumor patient cohort. Overall, our study provides the first single-cell analysis of the cellular and molecular differences between PL and LM in CRNELM patients. We identified distinct cell subsets and receptor-ligand interactions that may drive TME discrepancies and support metastatic tumor growth. These insights highlight potential therapeutic targets and inform strategies for better managing CRNELM patients.","PeriodicalId":19000,"journal":{"name":"Molecular Cancer","volume":"205 1","pages":""},"PeriodicalIF":37.3,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142991095","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tailoring traditional Chinese medicine in cancer therapy","authors":"Shuiquan Li, Xi Chen, Hui Shi, Ming Yi, Bing Xiong, Tianye Li","doi":"10.1186/s12943-024-02213-6","DOIUrl":"https://doi.org/10.1186/s12943-024-02213-6","url":null,"abstract":"Cancer remains a formidable global health challenge, necessitating innovative therapeutic approaches to enhance treatment efficacy and reduce adverse effects. The traditional Chinese medicine (TCM), as an embodiment of ancient wisdom, has been validated to regulate the holistic human capacity against both internal and external “evils” in accordance with TCM principles. Therefore, it stands to reason to integrate TCM into current cancer therapy paradigms, such as chemotherapy, immunotherapy, and targeted therapy. This strategy conceptually intends to circumvent the inevitable side effects derived from present treatment, alleviate the discomfort, mollify the detrimental mood and synergize tumoricidal effects of distinct approaches. However, it is still vague whether TCM exert favorable function in cancer treatment. Therefore, it is imperative to retrieve and compile the existing literature on TCM in the realm of cancer, followed by a comprehensive recapitulation and synthesis of its core findings. Recently, with the advancement of contemporary biologic and medical theory and technology, it has become both feasible and imperative to elucidate the molecular signaling mechanisms and cellular biology underlying TCM. Specifically, leveraging TCM pharmaceutic components can not only directly impact tumor biology at the molecular level, but regulate the tumor immune environment through distinct pathways. Additionally, the administration of external TCM treatments such as acupuncture and moxibustion also demonstrates beneficial effects in cancer patients. Through comprehensive analysis, we demonstrated that TCM not only potentially increases the efficacy of conventional cancer treatments, but also significantly mitigates their toxic side effects, thereby prolonging patients’ prognosis and improving their living quality. Furthermore, we have underscored the challenges and prospects associated with the integration of TCM into contemporary oncological practices, placing particular emphasis on the imperative for rigorous clinical trials and molecular investigations to substantiate the efficacy and safety of these combined therapeutic approaches. This synthesis aims to pave the way for a more integrated approach to cancer treatment rooted in both traditional wisdom and cutting-edge science.","PeriodicalId":19000,"journal":{"name":"Molecular Cancer","volume":"49 1","pages":""},"PeriodicalIF":37.3,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142991096","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Intercellular TIMP-1-CD63 signaling directs the evolution of immune escape and metastasis in KRAS-mutated pancreatic cancer cells","authors":"Chu-An Wang, Ya-Chin Hou, Yi-Kai Hong, Yu-Jing Tai, Chieh Shen, Pei-Chi Hou, Jhao-Lin Fu, Cheng-Lin Wu, Siao Muk Cheng, Daw-Yang Hwang, Yung-Yeh Su, Yan-Shen Shan, Shaw-Jenq Tsai","doi":"10.1186/s12943-024-02207-4","DOIUrl":"https://doi.org/10.1186/s12943-024-02207-4","url":null,"abstract":"Oncogenic KRAS mutations are present in approximately 90% of pancreatic ductal adenocarcinoma (PDAC). However, Kras mutation alone is insufficient to transform precancerous cells into metastatic PDAC. This study investigates how KRAS-mutated epithelial cells acquire the capacity to escape senescence or even immune clearance, thereby progressing to advanced PDAC. Single-cell RNA sequencing and analysis of primary PDAC tumors were conducted. Genetically engineered pancreas-specific Kras-mutated, dual specificity phosphatase-2 (Dusp2) knockout mouse models were established. Human and mouse primary pancreatic cancer cell lines were used for in vitro assessment of cancer characteristics. Tumor progression was studied via pancreas orthotopic and portal vein injection in the immune-competent mice. Clinical relevance was validated by digital spatial transcriptomic analysis of PDAC tumors. Kras mutation induces the formation of pancreatic intraepithelial neoplasia (PanIN), these lesions also exhibit significant apoptotic signals. Single-cell RNA sequencing identified a subset of ERKactiveDUSP2low cells continuing to expand from early to advanced stage PDAC. In vitro and in vivo studies reveal that early infiltrating macrophage-derived tissue inhibitor of metallopeptidase 1 (TIMP-1) is the key factor in maintaining the ERKactiveDUSP2low cell population in a CD63-dependent manner. The ERKactiveDUSP2low cancer cells further exacerbate macrophage-mediated cancer malignancy, including loss of epithelial trait, increased lymphangiogenesis, and immune escape. Digital spatial profiling analysis of PDAC samples demonstrates the colocalization of TIMP-1high macrophages and CD63high cancer cells. The presence of TIMP-1high macrophages and CD63high epithelial cells correlates with poor prognosis in PDAC. Our study reveals the vicious cycle between early infiltrating macrophages and pancreatic cancer cells, providing a mechanistic insight into the dynamic regulation directing pancreatic cancer progression.","PeriodicalId":19000,"journal":{"name":"Molecular Cancer","volume":"55 1","pages":""},"PeriodicalIF":37.3,"publicationDate":"2025-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142988894","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}