Cancer Science最新文献

{"title":"Delta-6 desaturase FADS2 is a tumor-promoting factor in cholangiocarcinoma","authors":"Kohsei Hasegawa,&nbsp;Haruna Fujimori,&nbsp;Kohta Nakatani,&nbsp;Masatomo Takahashi,&nbsp;Yoshihiro Izumi,&nbsp;Takeshi Bamba,&nbsp;Mao Nakamura-Shima,&nbsp;Rie Shibuya-Takahashi,&nbsp;Mai Mochizuki,&nbsp;Yuta Wakui,&nbsp;Makoto Abue,&nbsp;Wataru Iwai,&nbsp;Daisuke Fukushi,&nbsp;Kennichi Satoh,&nbsp;Kazunori Yamaguchi,&nbsp;Norihisa Shindo,&nbsp;Jun Yasuda,&nbsp;Naoki Asano,&nbsp;Takayuki Imai,&nbsp;Yukinori Asada,&nbsp;Yukio Katori,&nbsp;Keiichi Tamai","doi":"10.1111/cas.16306","DOIUrl":"10.1111/cas.16306","url":null,"abstract":"<p>Cholangiocarcinoma is a fatal disease with limited therapeutic options. We screened genes required for cholangiocarcinoma tumorigenicity and identified FADS2, a delta-6 desaturase. FADS2 depletion reduced in vivo tumorigenicity and cell proliferation. In clinical samples, FADS2 was expressed in cancer cells but not in stromal cells. FADS2 inhibition also reduced the migration and sphere-forming ability of cells and increased apoptotic cell death and ferroptosis markers. Lipidome assay revealed that triglyceride and cholesterol ester levels were decreased in FADS2-knockdown cells. The oxygen consumption ratio was also decreased in FADS2-depleted cells. These data indicate that FADS2 depletion causes a reduction in lipid levels, resulting in decrease of energy production and attenuation of cancer cell malignancy.</p>","PeriodicalId":9580,"journal":{"name":"Cancer Science","volume":"115 10","pages":"3346-3357"},"PeriodicalIF":4.5,"publicationDate":"2024-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11447924/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141903322","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Concerning trends and potential issues in osteosarcoma research publication","authors":"Keisuke Horiuchi,&nbsp;Kazuhiro Chiba","doi":"10.1111/cas.16303","DOIUrl":"10.1111/cas.16303","url":null,"abstract":"&lt;p&gt;Osteosarcoma is a rare malignant bone tumor affecting approximately 5 per million persons per year in children and adolescents. Despite this rarity, there has been a substantial increase in the number of publications on osteosarcoma research, especially those involving cell-based experiments (Figure 1A). Given this discrepancy between the potential increase in knowledge about this malignancy and the impeded improvement in clinical outcomes,&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt; we sought to understand the possible reasons for this difference and the trends in osteosarcoma research publications over the past decades.&lt;/p&gt;&lt;p&gt;We analyzed 416 basic research publications on human osteosarcoma (defined as papers with the term “osteosarcoma” in the title and the term “cell line” in the MeSH terms) published in 2020, around the year when the number of such publications peaked, to understand their content and identify potential issues. We found that publications from China (319 papers, 76.7%) far outnumbered those from other countries combined (97 papers, 23.3%), accounting for more than three-quarters of all publications this year (Figure 1B). As we went through these manuscripts, we noticed that a certain number of papers shared similar characteristics, including study design and figure layout and presentation. In addition to these subjective similarities, we also noticed more objective characteristics common to these papers. In particular, a significantly large proportion of the papers (41.1%) dealt with the potential functions of miRNAs, lncRNAs, or circRNAs in the pathology of osteosarcoma (Figure 1C). The overrepresentation of such papers (hereafter referred to as “miRNA/lncRNA” papers) is noteworthy because, although these molecules are known to play a critical role in some cancers, the evidence for the involvement of any particular miRNA or lncRNA in human osteosarcoma development is limited to date and is unlikely to represent the most critical avenues for current osteosarcoma research.&lt;span&gt;&lt;sup&gt;2&lt;/sup&gt;&lt;/span&gt;&lt;/p&gt;&lt;p&gt;Moreover, we found that these papers often used potentially problematic controls for the human osteosarcoma specimens and osteosarcoma cell lines. In particular, the use of “adjacent tissue” (also referred to as “normal tissue,” “para-tumor tissue,” “para-carcinoma tissue,” etc. in these papers) as a control for osteosarcoma specimens was found in 35.3% (147 out of 416) of the publications (Figure 1D). Because osteosarcoma patients typically undergo highly intensive preoperative chemotherapy, viable tumor specimens can only be obtained during biopsy. However, a biopsy is typically performed in a manner that minimizes contamination of surrounding tissues with tumor cells and pathologic fractures. Therefore, obtaining normal bone tissue at some distance from the lesion during biopsy is unfeasible and potentially unethical, as it can be detrimental to the patient. Bone tissue could be obtained during definitive surgery; however, gene expression pa","PeriodicalId":9580,"journal":{"name":"Cancer Science","volume":"115 10","pages":"3483-3485"},"PeriodicalIF":4.5,"publicationDate":"2024-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11447875/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141894700","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"N-acetylgalactosaminyltransferase GALNT6 is a potential therapeutic target of clear cell renal cell carcinoma progression","authors":"Luhaoran Sun,&nbsp;Zeyu Li,&nbsp;Peng Shu,&nbsp;Min Lu","doi":"10.1111/cas.16296","DOIUrl":"10.1111/cas.16296","url":null,"abstract":"<p>High expression of truncated O-glycans Tn antigen predicts adverse clinical outcome in patients with clear cell renal cell carcinoma (ccRCC). To understand the biosynthetic underpinnings of Tn antigen changes in ccRCC, we focused on N-acetylgalactosaminyltransferases (GALNTs, also known as GalNAcTs) known to be involved in Tn antigen synthesis. Data from GSE15641 profile and local cohort showed that GALNT6 was significantly upregulated in ccRCC tissues. The current study aimed to determine the role of GALNT6 in ccRCC, and whether GALNT6-mediated O-glycosylation aggravates malignant behaviors. Gain- and loss-of-function experiments showed that overexpression of GALNT6 accelerated ccRCC cell proliferation, migration, and invasion, as well as promoted ccRCC-derived xenograft tumor growth and lung metastasis. In line with this, silencing of GALNT6 yielded the opposite results. Mechanically, high expression of GALNT6 led to the accumulation of Tn antigen in ccRCC cells. By undertaking immunoprecipitation coupled with liquid chromatography/mass spectrometry, vicia villosa agglutinin blot, and site-directed mutagenesis assays, we found that O-glycosylation of prohibitin 2 (PHB2) at Ser161 was required for the GALNT6-induced ccRCC cell proliferation, migration, and invasion. Additionally, we identified lens epithelium-derived growth factor (LEDGF) as a key regulator of GALNT6 transcriptional induction in ccRCC growth and an upstream contributor to ccRCC aggressive behavior. Collectively, our findings indicate that GALNT6-mediated abnormal O-glycosylation promotes ccRCC progression, which provides a potential therapeutic target in ccRCC development.</p>","PeriodicalId":9580,"journal":{"name":"Cancer Science","volume":"115 10","pages":"3320-3332"},"PeriodicalIF":4.5,"publicationDate":"2024-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11447896/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141894701","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unveiling hierarchy and spatial distribution of O6-methylguanine-DNA methyltransferase promoter methylation in World Health Organization grade 2–3 gliomas","authors":"Mingxiao Li,&nbsp;Jiang Liu,&nbsp;Jiancong Weng,&nbsp;Gehong Dong,&nbsp;Xuzhu Chen,&nbsp;Yong Cui,&nbsp;Xiaohui Ren,&nbsp;Shaoping Shen,&nbsp;Haihui Jiang,&nbsp;Xiaokang Zhang,&nbsp;Xuzhe Zhao,&nbsp;Ming Li,&nbsp;Xijie Wang,&nbsp;Hongxiang Ren,&nbsp;Qiang Li,&nbsp;Yulian Zhang,&nbsp;Quan Cheng,&nbsp;Yanbing Yu,&nbsp;Song Lin","doi":"10.1111/cas.16268","DOIUrl":"10.1111/cas.16268","url":null,"abstract":"<p>This study investigated the role of O⁶-methylguanine-DNA methyltransferase promoter (MGMTp) methylation hierarchy and heterogeneity in grade 2–3 gliomas, focusing on variations in chemotherapy benefits and resection dependency. A cohort of 668 newly diagnosed grade 2–3 gliomas, with comprehensive clinical, radiological, and molecular data, formed the basis of this analysis. The extent of resection was categorized into gross total resection (GTR ≥100%), subtotal resection (STR &gt;90%), and partial resection (PR ≤90%). MGMTp methylation levels were examined using quantitative pyrosequencing. Our findings highlighted the critical role of GTR in improving the prognosis for astrocytomas (IDH1/2-mutant and 1p/19q non-codeleted), contrasting with its lesser significance for oligodendrogliomas (IDH1/2 mutation and 1p/19q codeletion). Oligodendrogliomas demonstrated the highest average MGMTp methylation levels (median: 28%), with a predominant percentage of methylated cases (average methylation levels &gt;20%). Astrocytomas were more common in the low-methylated group (10%–20%), while IDH wild-type gliomas were mostly unmethylated (&lt;10%). Spatial distribution analysis revealed a decrement in frontal lobe involvement from methylated, low-methylated to unmethylated cases (72.8%, 59.3%, and 47.8%, respectively). In contrast, low-methylated and unmethylated cases were more likely to invade the temporal-insular region (19.7%, 34.3%, and 40.4%, respectively). Astrocytomas with intermediate MGMTp methylation were notably associated with temporal-insular involvement, potentially indicating a moderate response to temozolomide and underscoring the importance of aggressive resection strategies. In conclusion, our study elucidates the complex interplay of MGMTp methylation hierarchy and heterogeneity among grade 2–3 gliomas, providing insights into why astrocytomas and IDH wild-type lower-grade glioma might derive less benefit from chemotherapy.</p>","PeriodicalId":9580,"journal":{"name":"Cancer Science","volume":"115 10","pages":"3403-3414"},"PeriodicalIF":4.5,"publicationDate":"2024-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11447971/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141890643","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"RETRACTION: Capn4 is a Marker of Poor Clinical Outcomes and Promotes Nasopharyngeal Carcinoma Metastasis via Nuclear Factor-κB-Induced Matrix Metalloproteinase 2 Expression","authors":"","doi":"10.1111/cas.16305","DOIUrl":"10.1111/cas.16305","url":null,"abstract":"<p><b>RETRACTION</b>: P.-C. Zheng, X. Chen, H.-W. Zhu, W. Zheng, L.-H. Mao, C. Lin, J.-N. Liu and M. Zheng, “Capn4 is a Marker of Poor Clinical Outcomes and Promotes Nasopharyngeal Carcinoma Metastasis via Nuclear Factor-κB-Induced Matrix Metalloproteinase 2 Expression,” <i>Cancer Science</i> 105, no. 6 (2014): 630–638, https://doi.org/10.1111/cas.12416.</p><p>The above article, published online on 07 April 2014 in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the journal Editor-in-Chief, Masanori Hatakeyama; Japanese Cancer Association; and John Wiley &amp; Sons Australia, Ltd. Following publication, concerns were raised by a third party regarding suspected overlap of elements within the western blot presented in Figure 3b and a figure published earlier in another paper elsewhere. Furthermore, image analysis uncovered several instances of overlap within the cell migration and cell invasion Transwell assay images presented in Figure 3c. The authors were unable to provide the original data and did not provide a satisfactory explanation for the overlaps. As a result, the article's conclusions can no longer be considered valid.</p>","PeriodicalId":9580,"journal":{"name":"Cancer Science","volume":"115 10","pages":"3491"},"PeriodicalIF":4.5,"publicationDate":"2024-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11448361/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141890642","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tumor-derived mitochondrial formyl peptides suppress tumor immunity through modification of the tumor microenvironment","authors":"Kayoko Waki,&nbsp;Miyako Ozawa,&nbsp;Keisuke Ohta,&nbsp;Nobukazu Komatsu,&nbsp;Akira Yamada","doi":"10.1111/cas.16266","DOIUrl":"10.1111/cas.16266","url":null,"abstract":"<p>Mitochondrial <i>N</i>-formylpeptides are released from damaged or dead cells to the extracellular spaces and cause inflammatory responses. The role of mitochondrial <i>N-</i>formylpeptides in aseptic systemic inflammatory response syndromes induced by trauma or cardiac surgery has been well investigated. However, there are no reports regarding the role of mitochondrial <i>N-</i>formylpeptides in cancer. In this study, we investigated the role of tumor cell-derived mitochondrial <i>N-</i>formylpeptides in anti-tumor immunity using knockout murine tumor cells of mitochondrial methionyl-tRNA formyltransferase (MTFMT), which catalyze <i>N-</i>formylation of mitochondrial DNA-encoded proteins. There was no apparent difference among the wild-type and MTFMT-knockout clones of E.G7-OVA cells with respect to morphology, mitochondrial dynamics, glycolysis and oxidative phosphorylation, oxygen consumption rate, or <i>in vitro</i> cell growth. In contrast, <i>in vivo</i> tumor growth of MTFMT-knockout cells was slower than that of wild-type cells. A reduced number of myeloid-derived suppressor cells and an increase of cytotoxic T-lymphocytes in the tumor tissues were observed in the MTFMT-knockout tumors. These results suggested that tumor cell-derived mitochondrial <i>N-</i>formylpeptides had a negative role in the host anti-tumor immunity through modification of the tumor microenvironment.</p>","PeriodicalId":9580,"journal":{"name":"Cancer Science","volume":"115 10","pages":"3218-3230"},"PeriodicalIF":4.5,"publicationDate":"2024-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11447925/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141861310","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multiplex plasma protein assays as a diagnostic tool for lung cancer","authors":"Mohammad Tanvir Ahamed,&nbsp;Jenny Forshed,&nbsp;Adrian Levitsky,&nbsp;Janne Lehtiö,&nbsp;Amanj Bajalan,&nbsp;Maria Pernemalm,&nbsp;Lars E. Eriksson,&nbsp;Björn Andersson","doi":"10.1111/cas.16300","DOIUrl":"10.1111/cas.16300","url":null,"abstract":"<p>Lack of the established noninvasive diagnostic biomarkers causes delay in diagnosis of lung cancer (LC). The aim of this study was to explore the association between inflammatory and cancer-associated plasma proteins and LC and thereby discover potential biomarkers. Patients referred for suspected LC and later diagnosed with primary LC, other cancers, or no cancer (NC) were included in this study. Demographic information and plasma samples were collected, and diagnostic information was later retrieved from medical records. Relative quantification of 92 plasma proteins was carried out using the Olink Immuno-Onc-I panel. Association between expression levels of panel of proteins with different diagnoses was assessed using generalized linear model (GLM) with the binomial family and a logit-link function, considering confounder effects of age, gender, smoking, and pulmonary diseases. The analysis showed that the combination of five plasma proteins (CD83, GZMA, GZMB, CD8A, and MMP12) has higher diagnostic performance for primary LC in both early and advanced stages compared with NC. This panel demonstrated lower diagnostic performance for other cancer types. Moreover, inclusion of four proteins (GAL9, PDCD1, CD4, and HO1) to the aforementioned panel significantly increased the diagnostic performance for primary LC in advanced stage as well as for other cancers. Consequently, the collective expression profiles of select plasma proteins, especially when analyzed in conjunction, might have the potential to distinguish individuals with LC from NC. This suggests their utility as predictive biomarkers for identification of LC patients. The synergistic application of these proteins as biomarkers could pave the way for the development of diagnostic tools for early-stage LC detection.</p>","PeriodicalId":9580,"journal":{"name":"Cancer Science","volume":"115 10","pages":"3439-3454"},"PeriodicalIF":4.5,"publicationDate":"2024-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11447887/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141856904","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MGMT protein expression is a reliable predictive biomarker for temozolomide-containing chemotherapy in osteosarcoma","authors":"Yoshinori Uchihara,&nbsp;Katsutsugu Umeda,&nbsp;Yosuke Yamada,&nbsp;Hiroaki Ito,&nbsp;Keiji Tasaka,&nbsp;Kiyotaka Isobe,&nbsp;Ryo Akazawa,&nbsp;Naoko Kawabata,&nbsp;Satoshi Saida,&nbsp;Itaru Kato,&nbsp;Hidefumi Hiramatsu,&nbsp;Takashi Noguchi,&nbsp;Akio Sakamoto,&nbsp;Yoshiki Arakawa,&nbsp;Ayumu Arakawa,&nbsp;Nobuyuki Yamamoto,&nbsp;Yosuke Hosoya,&nbsp;Suguru Uemura,&nbsp;Ken-ichiro Watanabe,&nbsp;Hideki Sano,&nbsp;Takashi Taga,&nbsp;Junko Takita","doi":"10.1111/cas.16297","DOIUrl":"10.1111/cas.16297","url":null,"abstract":"<p>The prognosis of patients with osteosarcoma who experience recurrence or progression (R/P) is extremely poor, and more effective and less toxic therapies are needed. In the current study, the clinical data of osteosarcoma patients who experienced R/P were retrospectively analyzed to verify the reliability of O-6-methylguanine-DNA methyltransferase (MGMT) protein expression or MGMT promoter methylation for predicting the response to off-label temozolomide (TMZ)-containing chemotherapy. Of the 30 evaluable patients, 9 (30%) showed no/low MGMT protein expression, whereas all 16 evaluable patients had unmethylated MGMT promoter irrespective of MGMT protein expression levels. Twenty-three patients received TMZ-containing chemotherapy for measurable lesions (<i>n</i> = 14) or as adjuvant therapy following resection of recurrent lesions (<i>n</i> = 9). Among 14 patients with radiologically measurable lesions, the objective response rate was higher in the MGMT no/low-expression group (50.0%) than in the MGMT intermediate/high-expression group with borderline significance (0%, <i>p</i> = 0.066). The 6-month progression-free survival (PFS) rate in patients with radiologically measurable lesions was significantly higher in the MGMT no/low-expression group (50.0%) than in the MGMT intermediate/high-expression group (0%, <i>p</i> = 0.036). In the multivariate analysis of the 23 patients receiving TMZ-containing chemotherapy, MGMT expression and disease status before TMZ-containing chemotherapy were significantly associated with PFS. No severe adverse effects were observed during TMZ-containing chemotherapy. MGMT protein expression, but not MGMT promoter methylation, could predict a favorable outcome in patients receiving TMZ-containing chemotherapy.</p>","PeriodicalId":9580,"journal":{"name":"Cancer Science","volume":"115 10","pages":"3394-3402"},"PeriodicalIF":4.5,"publicationDate":"2024-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11447881/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141856903","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction to “P68 RNA helicase promotes invasion of glioma cells through negatively regulating DUSP5”","authors":"","doi":"10.1111/cas.16301","DOIUrl":"10.1111/cas.16301","url":null,"abstract":"<p>Wang R, Bao HB, Du WZ, et al. P68 RNA helicase promotes invasion of glioma cells through negatively regulating DUSP5. <i>Cancer Sci</i>. 2019 Jan;110(1):107-117. doi: 10.1111/cas.13858</p><p>There were errors in Figure 4A and Figure 6E in the above article.</p><p>The authors apologize for the errors.</p>","PeriodicalId":9580,"journal":{"name":"Cancer Science","volume":"115 10","pages":"3495"},"PeriodicalIF":4.5,"publicationDate":"2024-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11447874/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141793848","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Blocking CXCR4–CARM1–YAP axis overcomes osteosarcoma doxorubicin resistance by suppressing aerobic glycolysis","authors":"Zihua Li,&nbsp;Hengli Lu,&nbsp;Yiwei Zhang,&nbsp;Jiyang Lv,&nbsp;Yi Zhang,&nbsp;Tianyang Xu,&nbsp;Dong Yang,&nbsp;Zhengwei Duan,&nbsp;Yonghao Guan,&nbsp;Zongrui Jiang,&nbsp;Kaiyuan Liu,&nbsp;Yuxin Liao","doi":"10.1111/cas.16295","DOIUrl":"10.1111/cas.16295","url":null,"abstract":"<p>Osteosarcoma, recognized for its aggressiveness and resistance to chemotherapy, notably doxorubicin, poses significant treatment challenges. This comprehensive study investigated the CXCR4–CARM1–YAP signaling axis and its pivotal function in controlling aerobic glycolysis, which plays a crucial role in doxorubicin resistance. Detailed analysis of Dox-resistant 143b/MG63-DoxR cells has uncovered the overexpression of CXCR4. Utilizing a combination of molecular biology techniques including gene silencing, aerobic glycolysis assays such as Seahorse experiments, RNA sequencing, and immunofluorescence staining. The study provides insight into the mechanistic pathways involved. Results demonstrated that disrupting CXCR4 expression sensitizes cells to doxorubicin-induced apoptosis and alters glycolytic activity. Further RNA sequencing revealed that CARM1 modulated this effect through its influence on glycolysis, with immunofluorescence of clinical samples confirming the overexpression of CXCR4 and CARM1 in drug-resistant tumors. Chromatin immunoprecipitation studies further highlighted the role of CARM1, showing it to be regulated by methylation at the H3R17 site, which in turn affected YAP expression. Crucially, <i>in vivo</i> experiments illustrated that CARM1 overexpression could counteract the tumor growth suppression that resulted from CXCR4 inhibition. These insights revealed the intricate mechanisms at play in osteosarcoma resistance to doxorubicin and pointed toward potential new therapeutic strategies that could target this metabolic and signaling network to overcome drug resistance and improve patient outcomes.</p>","PeriodicalId":9580,"journal":{"name":"Cancer Science","volume":"115 10","pages":"3305-3319"},"PeriodicalIF":4.5,"publicationDate":"2024-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11447900/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141789605","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}