OncogenesisPub Date : 2023-05-06DOI: 10.1038/s41389-023-00471-5
Ruyu Yan, Dan Liu, Junjie Wang, Minxia Liu, Hongjuan Guo, Jing Bai, Shuo Yang, Jun Chang, Zhihong Yao, Zuozhang Yang, Tomas Blom, Kecheng Zhou
{"title":"miR-137-LAPTM4B regulates cytoskeleton organization and cancer metastasis via the RhoA-LIMK-Cofilin pathway in osteosarcoma.","authors":"Ruyu Yan, Dan Liu, Junjie Wang, Minxia Liu, Hongjuan Guo, Jing Bai, Shuo Yang, Jun Chang, Zhihong Yao, Zuozhang Yang, Tomas Blom, Kecheng Zhou","doi":"10.1038/s41389-023-00471-5","DOIUrl":"https://doi.org/10.1038/s41389-023-00471-5","url":null,"abstract":"<p><p>Osteosarcoma (OS) is a rare malignant bone tumor but is one leading cause of cancer mortality in childhood and adolescence. Cancer metastasis accounts for the primary reason for treatment failure in OS patients. The dynamic organization of the cytoskeleton is fundamental for cell motility, migration, and cancer metastasis. Lysosome Associated Protein Transmembrane 4B (LAPTM4B) is an oncogene participating in various biological progress central to cancer biogenesis. However, the potential roles of LAPTM4B in OS and the related mechanisms remain unknown. Here, we established the elevated LAPTM4B expression in OS, and it is essential in regulating stress fiber organization through RhoA-LIMK-cofilin signaling pathway. In terms of mechanism, our data revealed that LAPTM4B promotes RhoA protein stability by suppressing the ubiquitin-mediated proteasome degradation pathway. Moreover, our data show that miR-137, rather than gene copy number and methylation status, contributes to the upregulation of LAPTM4B in OS. We report that miR-137 is capable of regulating stress fiber arrangement, OS cell migration, and metastasis via targeting LAPTM4B. Combining results from cells, patients' tissue samples, the animal model, and cancer databases, this study further suggests that the miR-137-LAPTM4B axis represents a clinically relevant pathway in OS progression and a viable target for novel therapeutics.</p>","PeriodicalId":19489,"journal":{"name":"Oncogenesis","volume":"12 1","pages":"25"},"PeriodicalIF":6.2,"publicationDate":"2023-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10163001/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9797994","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":"Vortioxetine hydrobromide inhibits the growth of gastric cancer cells in vivo and in vitro by targeting JAK2 and SRC.","authors":"Mingzhu Li, Lina Duan, Wenjie Wu, Wenjing Li, Lili Zhao, Ang Li, Xuebo Lu, Xinyu He, Zigang Dong, Kangdong Liu, Yanan Jiang","doi":"10.1038/s41389-023-00472-4","DOIUrl":"https://doi.org/10.1038/s41389-023-00472-4","url":null,"abstract":"<p><p>Gastric cancer is the fourth leading cause of cancer deaths worldwide. Most patients are diagnosed in the advanced stage. Inadequate therapeutic strategies and the high recurrence rate lead to the poor 5-year survival rate. Therefore, effective chemopreventive drugs for gastric cancer are urgently needed. Repurposing clinical drugs is an effective strategy for discovering cancer chemopreventive drugs. In this study, we find that vortioxetine hydrobromide, an FDA-approved drug, is a dual JAK2/SRC inhibitor, and has inhibitory effects on cell proliferation of gastric cancer. Computational docking analysis, pull-down assay, cellular thermal shift assay (CETSA) and in vitro kinase assays are used to illustrate vortioxetine hydrobromide directly binds to JAK2 and SRC kinases and inhibits their kinase activities. The results of non-reducing SDS-PAGE and Western blotting indicate that vortioxetine hydrobromide suppresses STAT3 dimerization and nuclear translocation activity. Furthermore, vortioxetine hydrobromide inhibits the cell proliferation dependent on JAK2 and SRC and suppresses the growth of gastric cancer PDX model in vivo. These data demonstrate that vortioxetine hydrobromide, as a novel dual JAK2/SRC inhibitor, curbs the growth of gastric cancer in vitro and in vivo by JAK2/SRC-STAT3 signaling pathways. Our results highlight that vortioxetine hydrobromide has the potential application in the chemoprevention of gastric cancer.</p>","PeriodicalId":19489,"journal":{"name":"Oncogenesis","volume":"12 1","pages":"24"},"PeriodicalIF":6.2,"publicationDate":"2023-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10163056/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9797996","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}
OncogenesisPub Date : 2023-05-02DOI: 10.1038/s41389-023-00467-1
Carlos Matellan, Dariusz Lachowski, Ernesto Cortes, Kai Ning Chiam, Aleksandar Krstic, Stephen D Thorpe, Armando E Del Río Hernández
{"title":"Retinoic acid receptor β modulates mechanosensing and invasion in pancreatic cancer cells via myosin light chain 2.","authors":"Carlos Matellan, Dariusz Lachowski, Ernesto Cortes, Kai Ning Chiam, Aleksandar Krstic, Stephen D Thorpe, Armando E Del Río Hernández","doi":"10.1038/s41389-023-00467-1","DOIUrl":"https://doi.org/10.1038/s41389-023-00467-1","url":null,"abstract":"<p><p>Pancreatic ductal adenocarcinoma (PDAC) is the most common and lethal form of pancreatic cancer, characterised by stromal remodelling, elevated matrix stiffness and high metastatic rate. Retinoids, compounds derived from vitamin A, have a history of clinical use in cancer for their anti-proliferative and differentiation effects, and more recently have been explored as anti-stromal therapies in PDAC for their ability to induce mechanical quiescence in cancer associated fibroblasts. Here, we demonstrate that retinoic acid receptor β (RAR-β) transcriptionally represses myosin light chain 2 (MLC-2) expression in pancreatic cancer cells. As a key regulatory component of the contractile actomyosin machinery, MLC-2 downregulation results in decreased cytoskeletal stiffness and traction force generation, impaired response to mechanical stimuli via mechanosensing and reduced ability to invade through the basement membrane. This work highlights the potential of retinoids to target the mechanical drivers of pancreatic cancer.</p>","PeriodicalId":19489,"journal":{"name":"Oncogenesis","volume":"12 1","pages":"23"},"PeriodicalIF":6.2,"publicationDate":"2023-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10154384/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9465718","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}
OncogenesisPub Date : 2023-04-20DOI: 10.1038/s41389-023-00468-0
Jie Zhou, Guanming Chen, Jiuling Wang, Bo Zhou, Xuemin Sun, Jinsong Wang, Shu Tang, Xiangju Xing, Xiaofei Hu, Yang Zhao, Yu Peng, Wenjiong Shi, Tingting Zhao, Yuzhang Wu, Hanbing Zhong, Ni Hong, Zhihua Ruan, Yi Zhang, Wenfei Jin
{"title":"Anti-PD-1 therapy achieves favorable outcomes in HBV-positive non-liver cancer.","authors":"Jie Zhou, Guanming Chen, Jiuling Wang, Bo Zhou, Xuemin Sun, Jinsong Wang, Shu Tang, Xiangju Xing, Xiaofei Hu, Yang Zhao, Yu Peng, Wenjiong Shi, Tingting Zhao, Yuzhang Wu, Hanbing Zhong, Ni Hong, Zhihua Ruan, Yi Zhang, Wenfei Jin","doi":"10.1038/s41389-023-00468-0","DOIUrl":"https://doi.org/10.1038/s41389-023-00468-0","url":null,"abstract":"<p><p>Anti-PD-1 therapy has shown promising outcomes in the treatment of different types of cancer. It is of fundamental interest to analyze the efficacy of anti-PD-1 therapy in cancer patients infected with hepatitis B virus (HBV) since the comorbidity of HBV and cancer is widely documented. We designed a multicenter retrospective study to evaluate the efficacy of anti-PD-1 therapy on non-liver cancer patients infected with HBV. We found anti-PD-1 therapy achieved much better outcomes in HBV+ non-liver cancer patients than their HBV- counterparts. We performed single-cell RNA sequencing (scRNA-seq) on peripheral blood mononuclear cells (PBMCs) from esophageal squamous cell carcinoma (ESCC) patients. We found both cytotoxicity score of T cells and MHC score of B cells significantly increased after anti-PD-1 therapy in HBV+ ESCC patients. We also identified CX3CR1<sup>high</sup> T<sub>EFF</sub>, a subset of CD8<sup>+</sup> T<sub>EFF</sub>, associated with better clinical outcome in HBV+ ESCC patients. Lastly, we found CD8<sup>+</sup> T<sub>EFF</sub> from HBV+ ESCC patients showing higher fraction of Exhaustion<sup>hi</sup> T than their HBV- counterpart. In summary, anti-PD-1 therapy on HBV+ non-liver cancer patients is safe and achieves better outcomes than that on HBV- non-liver cancer patients, potentially because HBV+ patients had higher fraction of Exhaustion<sup>hi</sup> T, which made them more efficiently respond to anti-PD-1 therapy.</p>","PeriodicalId":19489,"journal":{"name":"Oncogenesis","volume":"12 1","pages":"22"},"PeriodicalIF":6.2,"publicationDate":"2023-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10119302/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9476763","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":"Exploring potential molecular resistance and clonal evolution in advanced HER2-positive gastric cancer under trastuzumab therapy.","authors":"Qi Xu, Xiaoqing Xu, Haimeng Tang, Junrong Yan, Jingjing Li, Hua Bao, Xue Wu, Yang Shao, Cong Luo, Haimin Wen, Jianying Jin, Jieer Ying","doi":"10.1038/s41389-023-00466-2","DOIUrl":"https://doi.org/10.1038/s41389-023-00466-2","url":null,"abstract":"<p><p>HER2-positive gastric cancer (GC) makes up 15-20% of all GC incidences, and targeted therapy with trastuzumab is the standard of treatment. However, the mechanisms of resistance to trastuzumab are still not fully understood and presents a significant challenge in clinical practice. In this study, whole exome sequencing (WES) was performed on paired tumor tissues before trastuzumab treatment (at baseline) and at progressive disease (PD) in 23 GC patients. Clinicopathological and molecular features that may be associated with primary and/or acquired resistance to trastuzumab were identified. Lauren classification of intestinal type was associated with a more prolonged progression-free survival (PFS) than diffuse type (HR = 0.29, P = 0.019). Patients with low tumor mutation burden (TMB) showed significantly worse PFS, while high chromosome instability (CIN) was correlated with prolonged OS (HR = 0.27; P = 0.044). Patients who responded to treatment had a higher CIN than nonresponders, and a positive trend towards increasing CIN was observed as response improved (P = 0.019). In our cohort, the most common genes to acquire mutations are AURKA, MYC, STK11, and LRP6 with four patients each. We also discovered an association between clonal branching pattern and survival, with an extensive clonal branching pattern being more closely related to a shorter PFS than other branching patterns (HR = 4.71; P = 0.008). We identified potential molecular and clinical factors that provide insight regarding potential association to trastuzumab resistance in advanced HER2-positive GC patients.</p>","PeriodicalId":19489,"journal":{"name":"Oncogenesis","volume":"12 1","pages":"21"},"PeriodicalIF":6.2,"publicationDate":"2023-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10113330/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9412891","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}
OncogenesisPub Date : 2023-04-12DOI: 10.1038/s41389-023-00465-3
Natalia Martínez, Teresa Gragera, María Pilar de Lucas, Ana Belén Cámara, Alicia Ballester, Berta Anta, Alberto Fernández-Medarde, Tania López-Briones, Judith Ortega, Daniel Peña-Jiménez, Antonio Barbáchano, Ana Montero-Calle, Víctor Cordero, Rodrigo Barderas, Teresa Iglesias, Mónica Yunta, José Luís Oliva, Alberto Muñoz, Eugenio Santos, Natasha Zarich, José M Rojas-Cabañeros
{"title":"PKD phosphorylation and COP9/Signalosome modulate intracellular Spry2 protein stability.","authors":"Natalia Martínez, Teresa Gragera, María Pilar de Lucas, Ana Belén Cámara, Alicia Ballester, Berta Anta, Alberto Fernández-Medarde, Tania López-Briones, Judith Ortega, Daniel Peña-Jiménez, Antonio Barbáchano, Ana Montero-Calle, Víctor Cordero, Rodrigo Barderas, Teresa Iglesias, Mónica Yunta, José Luís Oliva, Alberto Muñoz, Eugenio Santos, Natasha Zarich, José M Rojas-Cabañeros","doi":"10.1038/s41389-023-00465-3","DOIUrl":"https://doi.org/10.1038/s41389-023-00465-3","url":null,"abstract":"<p><p>Spry2 is a molecular modulator of tyrosine kinase receptor signaling pathways that has cancer-type-specific effects. Mammalian Spry2 protein undergoes tyrosine and serine phosphorylation in response to growth factor stimulation. Spry2 expression is distinctly altered in various cancer types. Inhibition of the proteasome functionality results in reduced intracellular Spry2 degradation. Using in vitro and in vivo assays, we show that protein kinase D (PKD) phosphorylates Spry2 at serine 112 and interacts in vivo with the C-terminal half of this protein. Importantly, missense mutation of Ser112 decreases the rate of Spry2 intracellular protein degradation. Either knocking down the expression of all three mammalian PKD isoforms or blocking their kinase activity with a specific inhibitor contributes to the stabilization of Spry2 wild-type protein. Downregulation of CSN3, a component of the COP9/Signalosome that binds PKD, significantly increases the half-life of Spry2 wild-type protein but does not affect the stability of a Spry2 after mutating Ser112 to the non-phosphorylatable residue alanine. Our data demonstrate that both PKD and the COP9/Signalosome play a significant role in control of Spry2 intracellular stability and support the consideration of the PKD/COP9 complex as a potential therapeutic target in tumors where Spry2 expression is reduced.</p>","PeriodicalId":19489,"journal":{"name":"Oncogenesis","volume":"12 1","pages":"20"},"PeriodicalIF":6.2,"publicationDate":"2023-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10097667/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9305570","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":"ACT001 inhibited CD133 transcription by targeting and inducing Olig2 ubiquitination degradation.","authors":"Huiting Deng, Hailin Liu, Guoyue Yang, Dandan Wang, Ying Luo, Chenglong Li, Zhenchang Qi, Zhili Liu, Peng Wang, Yanfang Jia, Yingtang Gao, Yahui Ding","doi":"10.1038/s41389-023-00462-6","DOIUrl":"https://doi.org/10.1038/s41389-023-00462-6","url":null,"abstract":"<p><p>Lung cancer is the most lethal malignancies with high aggressive and poor prognosis. Until now, the five-year survival rate has not been improved which brings serious challenge to human health. Lung cancer stem cells (LCSCs) serve as the root of cancer occurrence, progression, recurrence, and drug resistance. Therefore, effective anti-cancer agents and molecular mechanisms which could specifically eliminate LCSCs are urgently needed for drug design. In this article, we discovered Olig2 was overexpressed in clinical lung cancer tissues and acted as a transcription factor to regulate cancer stemness by regulating CD133 gene transcription. The results suggested Olig2 could be a promising target in anti-LCSCs therapy and new drugs targeted Olig2 may exhibit excellent clinical results. Furthermore, we verified ACT001, a guaianolide sesquiterpene lactone in phase II clinical trial with excellent glioma remission, inhibited cancer stemness by directly binding to Olig2 protein, inducing Olig2 ubiquitination degradation and inhibiting CD133 gene transcription. All these results suggested that Olig2 could be an excellent druggable target in anti-LCSCs therapy and lay a foundation for the further application of ACT001 in the treatment of lung cancer in clinical.</p>","PeriodicalId":19489,"journal":{"name":"Oncogenesis","volume":"12 1","pages":"19"},"PeriodicalIF":6.2,"publicationDate":"2023-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10060425/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9224921","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":"Transgelin promotes lung cancer progression via activation of cancer-associated fibroblasts with enhanced IL-6 release.","authors":"Chanjun Sun, Kaishang Zhang, Chen Ni, Jiajia Wan, Xixi Duan, Xiaohan Lou, Xiaohan Yao, Xiangnan Li, Ming Wang, Zhuoyu Gu, Pengyuan Yang, Zhenzhen Li, Zhihai Qin","doi":"10.1038/s41389-023-00463-5","DOIUrl":"https://doi.org/10.1038/s41389-023-00463-5","url":null,"abstract":"<p><p>Cancer-associated fibroblasts (CAFs), the principal constituent of the heterogenous tumor microenvironment, have been shown to promote tumor progression; however, the underlying mechanism is still less clear. Here, we find that transgelin (TAGLN) protein levels increased in primary CAFs isolated from human lung cancer, compared with those in paired normal fibroblasts. Tumor microarrays (TMAs) revealed that increased stromal TAGLN levels correlates with more lymphatic metastasis of tumor cells. In a subcutaneous tumor transplantation model, overexpression of Tagln in fibroblasts also increased tumor cell spread in mice. Further experiments show that Tagln overexpression promoted fibroblast activation and mobility in vitro. And TAGLN facilitates p-p65 entry into the nucleus, thereby activating the NF-κB signaling pathway in fibroblasts. Activated fibroblasts promote lung cancer progression via enhancing the release of pro-inflammatory cytokines, especially interleukine-6 (IL-6). Our study revealed that the high levels of stromal TAGLN is a predictive risk factor for patients with lung cancer. Targeting stromal TAGLN may present an alternative therapeutic strategy against lung cancer progression.</p>","PeriodicalId":19489,"journal":{"name":"Oncogenesis","volume":"12 1","pages":"18"},"PeriodicalIF":6.2,"publicationDate":"2023-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10060230/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9229478","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}
OncogenesisPub Date : 2023-03-28DOI: 10.1038/s41389-023-00464-4
Yu Tang, Wenfang Li, Li Qiu, Xia Zhang, Lei Zhang, Makoto Miyagishi, Hezhao Zhao, Shourong Wu, Vivi Kasim
{"title":"The p52-ZER6/G6PD axis alters aerobic glycolysis and promotes tumor progression by activating the pentose phosphate pathway.","authors":"Yu Tang, Wenfang Li, Li Qiu, Xia Zhang, Lei Zhang, Makoto Miyagishi, Hezhao Zhao, Shourong Wu, Vivi Kasim","doi":"10.1038/s41389-023-00464-4","DOIUrl":"https://doi.org/10.1038/s41389-023-00464-4","url":null,"abstract":"<p><p>Abnormal glucose metabolism is a highlight of tumor metabolic reprogramming and is closely related to the development of malignancies. p52-ZER6, a C<sub>2</sub>H<sub>2</sub>-type zinc finger protein, promotes cell proliferation and tumorigenesis. However, its role in the regulation of biological and pathological functions remains poorly understood. Here, we examined the role of p52-ZER6 in tumor cell metabolic reprogramming. Specifically, we demonstrated that p52-ZER6 promotes tumor glucose metabolic reprogramming by positively regulating the transcription of glucose-6-phosphate dehydrogenase (G6PD), the rate-limiting enzyme in the pentose phosphate pathway (PPP). By activating the PPP, p52-ZER6 was found to enhance the production of nucleotides and nicotinamide adenine dinucleotide phosphate, thereby providing tumor cells with the building blocks of ribonucleic acids and cellular reductants for reactive oxygen species scavenging, which subsequently promotes tumor cell proliferation and viability. Importantly, p52-ZER6 promoted PPP-mediated tumorigenesis in a p53-independent manner. Taken together, these findings reveal a novel role for p52-ZER6 in regulating G6PD transcription via a p53-independent process, ultimately resulting in tumor cell metabolic reprogramming and tumorigenesis. Our results suggest that p52-ZER6 is a potential target for the diagnosis and treatment of tumors and metabolic disorders.</p>","PeriodicalId":19489,"journal":{"name":"Oncogenesis","volume":"12 1","pages":"17"},"PeriodicalIF":6.2,"publicationDate":"2023-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10050210/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9211687","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}
OncogenesisPub Date : 2023-03-18DOI: 10.1038/s41389-023-00460-8
Dimitri Vanauberg, Céline Schulz, Tony Lefebvre
{"title":"Involvement of the pro-oncogenic enzyme fatty acid synthase in the hallmarks of cancer: a promising target in anti-cancer therapies.","authors":"Dimitri Vanauberg, Céline Schulz, Tony Lefebvre","doi":"10.1038/s41389-023-00460-8","DOIUrl":"https://doi.org/10.1038/s41389-023-00460-8","url":null,"abstract":"<p><p>An accelerated de novo lipogenesis (DNL) flux is a common characteristic of cancer cells required to sustain a high proliferation rate. The DNL enzyme fatty acid synthase (FASN) is overexpressed in many cancers and is pivotal for the increased production of fatty acids. There is increasing evidences of the involvement of FASN in several hallmarks of cancer linked to its ability to promote cell proliferation via membranes biosynthesis. In this review we discuss about the implication of FASN in the resistance to cell death and in the deregulation of cellular energetics by increasing nucleic acids, protein and lipid synthesis. FASN also promotes cell proliferation, cell invasion, metastasis and angiogenesis by enabling the building of lipid rafts and consequently to the localization of oncogenic receptors such as HER2 and c-Met in membrane microdomains. Finally, FASN is involved in immune escape by repressing the activation of pro-inflammatory cells and promoting the recruitment of M2 macrophages and T regulatory cells in the tumor microenvironment. Here, we provide an overview of the involvement of the pro-oncogenic enzyme in the hallmarks of cancer making FASN a promising target in anti-cancer therapy to circumvent resistance to chemotherapies.</p>","PeriodicalId":19489,"journal":{"name":"Oncogenesis","volume":"12 1","pages":"16"},"PeriodicalIF":6.2,"publicationDate":"2023-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10024702/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9199026","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}
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