المؤلفون: Zeng, Qinru, Zeng, Shaocheng, Dai, Xiaofeng, Ding, Yun, Huang, Chunye, Ruan, Ruiwen, Xiong, Jianping, Tang, Xiaomei, Deng, Jun

المساهمون: National Natural Science Foundation of China

المصدر: Genes & Diseases ; page 101279 ; ISSN 2352-3042

مصطلحات موضوعية: Cell Biology, Genetics (clinical), Molecular Biology, Biochemistry

الإتاحة: https://doi.org/10.1016/j.gendis.2024.101279Test
https://api.elsevier.com/content/article/PII:S235230422400076X?httpAccept=text/xmlTest
https://api.elsevier.com/content/article/PII:S235230422400076X?httpAccept=text/plainTest

المؤلفون: Ruan, Ruiwen, Li, Li, Li, Xuan, Huang, Chunye, Zhang, Zhanmin, Zhong, Hongguang, Zeng, Shaocheng, Shi, Qianqian, Xia, Yang, Zeng, Qinru, Wen, Qin, Chen, Jingyi, Dai, Xiaofeng, Xiong, Jianping, Xiang, Xiaojun, Lei, Wan, Deng, Jun

المساهمون: Natural Science Foundation of Jiangxi Province, Government of Jiangxi Province, Jiangxi Provincial Department of Science and Technology, Foundation of Jiangxi Educational Commission, National Natural Science Foundation of China, Youth Science Foundation of Jiangxi Province

المصدر: Molecular Cancer ; volume 22, issue 1 ; ISSN 1476-4598

مصطلحات موضوعية: Cancer Research, Oncology, Molecular Medicine

الوصف: Background Fibroblast growth factors (FGFs) and their receptors (FGFRs) play a crucial role in cell fate and angiogenesis, with dysregulation of the signaling axis driving tumorigenesis. Therefore, many studies have targeted FGF/FGFR signaling for cancer therapy and several FGFR inhibitors have promising results in different tumors but treatment efficiency may still be improved. The clinical use of immune checkpoint blockade (ICB) has resulted in sustained remission for patients. Main Although there is limited data linking FGFR inhibitors and immunotherapy, preclinical research suggest that FGF/FGFR signaling is involved in regulating the tumor microenvironment (TME) including immune cells, vasculogenesis, and epithelial-mesenchymal transition (EMT). This raises the possibility that ICB in combination with FGFR-tyrosine kinase inhibitors (FGFR-TKIs) may be feasible for treatment option for patients with dysregulated FGF/FGFR signaling. Conclusion Here, we review the role of FGF/FGFR signaling in TME regulation and the potential mechanisms of FGFR-TKI in combination with ICB. In addition, we review clinical data surrounding ICB alone or in combination with FGFR-TKI for the treatment of FGFR-dysregulated tumors, highlighting that FGFR inhibitors may sensitize the response to ICB by impacting various stages of the “cancer-immune cycle”.

الإتاحة: https://doi.org/10.1186/s12943-023-01761-7Test

المؤلفون: Dai, Xiaofeng, Wu, Zhipeng, Ruan, Ruiwen, Chen, Jingyi, Huang, Chunye, Lei, Wan, Yao, Yangyang, Li, Li, Tang, Xiaomei, Xiong, Jianping, Feng, Miao, Deng, Jun

المصدر: Cell Communication & Signaling; 3/7/2024, Vol. 22 Issue 1, p1-19, 19p

مصطلحات موضوعية: PROGRAMMED death-ligand 1, COLORECTAL cancer, T cells, TUMOR growth, CELL death

مستخلص: Background: The effectiveness of anti-programmed cell death protein 1(PD-1)/programmed cell death 1 ligand 1(PD-L1) therapy in treating certain types of cancer is associated with the level of PD-L1. However, this relationship has not been observed in colorectal cancer (CRC), and the underlying regulatory mechanism of PD-L1 in CRC remains unclear. Methods: Binding of TMEM160 to PD-L1 was determined by co-immunoprecipitation (Co-IP) and GST pull-down assay.The ubiquitination levels of PD-L1 were verified using the ubiquitination assay. Phenotypic experiments were conducted to assess the role of TMEM160 in CRC cells. Animal models were employed to investigate how TMEM160 contributes to tumor growth.The expression and clinical significance of TMEM160 and PD-L1 in CRC tissues were evaluated by immunohistochemistry(IHC). Results: In our study, we made a discovery that TMEM160 interacts with PD-L1 and plays a role in stabilizing its expression within a CRC model. Furthermore, we demonstrated that TMEM160 hinders the ubiquitination-dependent degradation of PD-L1 by competing with SPOP for binding to PD-L1 in CRC cells. Regarding functionality, the absence of TMEM160 significantly inhibited the proliferation, invasion, metastasis, clonogenicity, and radioresistance of CRC cells, while simultaneously enhancing the cytotoxic effect of CD8 + T cells on tumor cells. Conversely, the upregulation of TMEM160 substantially increased these capabilities. In severely immunodeficient mice, tumor growth derived from lentiviral vector shTMEM160 cells was lower compared with that derived from shNC control cells. Furthermore, the downregulation of TMEM160 significantly restricted tumor growth in immune-competent BALB/c mice. In clinical samples from patients with CRC, we observed a strong positive correlation between TMEM160 expression and PD-L1 expression, as well as a negative correlation with CD8A expression. Importantly, patients with high TMEM160 expression exhibited a worse prognosis compared with those with low or no TMEM160 expression. Conclusions: Our study reveals that TMEM160 inhibits the ubiquitination-dependent degradation of PD-L1 that is mediated by SPOP, thereby stabilizing PD-L1 expression to foster the malignant progress, radioresistance, and immune evasion of CRC cells. These findings suggest that TMEM160 holds potential as a target for the treatment of patients with CRC. [ABSTRACT FROM AUTHOR]

: Copyright of Cell Communication & Signaling is the property of BioMed Central and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

المؤلفون: Yao, Yangyang, Liu, Zhen, Huang, Shanshan, Huang, Chunye, Cao, Yuan, Li, Li, Guo, Hui, Liu, Fenfen, Huang, Shipeng, Liao, Quan, He, Xin, Chen, Jun, Li, Junhe, Xiang, Xiaojun, Xiong, Jianping, Deng, Jun

المصدر: Cell Death Discovery ; volume 8, issue 1 ; ISSN 2058-7716

مصطلحات موضوعية: Cancer Research, Cell Biology, Cellular and Molecular Neuroscience, Immunology

الوصف: F-box and WD repeat domain-containing 5 (FBXW5), with WD40 repeats, can bind to the PPxY sequence of the large tumor suppressor kinases 1/2 (LATS1/2) kinase domain, resulting in ubiquitination. Ubiquitination and the subsequent degradation of LATS1/2 abrogate the Hippo pathway and worsen gastric cancer (GC). However, the effects and molecular mechanisms of FBXW5 in GC remain unexplored. To elucidate the clinical significance of FBXW5, immunohistochemistry was conducted to reveal the positive correlation between FBXW5 expression and lymph node metastasis ( p < 0.001) and TNM stage (training cohort: p = 0.018; validation cohort: p = 0.001). Further, patients with high FBXW5 expression were found to have poor prognosis (training cohort: log-rank p = 0.020; validation cohort: log-rank p = 0.025). Cell experiments revealed the promoting effects of FBXW5 on the proliferation, invasion, metastasis, and chemoresistance of GC cells. Blocking LATS1-YAP1 leads to the loss of FBXW5-mediated regulation of the Hippo pathway and partial functions. Further, co-immunoprecipitation and in vivo ubiquitination assays revealed the interaction between FBXW5 and LATS1, which promoted the ubiquitination and degradation of LATS1. Based on mouse xenograft assays, FBXW5 silencing attenuated the growth of subcutaneous tumor xenografts. Altogether, FBXW5 was found to inactivate the Hippo signaling pathway by enhancing LATS1 ubiquitination and degradation, which promoted the invasion, metastasis, and drug resistance of GC cells.

الإتاحة: https://doi.org/10.1038/s41420-022-00868-yTest
https://www.nature.com/articles/s41420-022-00868-y.pdfTest
https://www.nature.com/articles/s41420-022-00868-yTest

المؤلفون: Huang, Chunye, Wen, Qin, Chen, Jingyi, Zhong, Hongguang, Xiang, Xiaojun, Xiong, Jianping, Deng, Jun

المصدر: Cancer Treatment and Research Communications ; volume 31, page 100568 ; ISSN 2468-2942

مصطلحات موضوعية: Cancer Research, Oncology

الإتاحة: https://doi.org/10.1016/j.ctarc.2022.100568Test
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المؤلفون: Li, Xuan, Zhong, Hongguang, Shi, Qianqian, Ruan, Ruiwen, Huang, Chunye, Wen, Qin, Zeng, Shaocheng, Xia, Yang, Zeng, Qinru, Xiong, Jianping, Wang, Shanshan, Chen, Jun, Lei, Wan, Deng, Jun

المصدر: Cellular & Molecular Life Sciences; Jan2024, Vol. 81 Issue 1, p1-19, 19p

مستخلص: Hippo-Yes-associated protein 1 (YAP1) plays an important role in gastric cancer (GC) progression; however, its regulatory network remains unclear. In this study, we identified Copine III (CPNE3) was identified as a novel direct target gene regulated by the YAP1/TEADs transcription factor complex. The downregulation of CPNE3 inhibited proliferation and invasion, and increased the chemosensitivity of GC cells, whereas the overexpression of CPNE3 had the opposite biological effects. Mechanistically, CPNE3 binds to the YAP1 protein in the cytoplasm, inhibiting YAP1 ubiquitination and degradation mediated by the E3 ubiquitination ligase β-transducin repeat-containing protein (β-TRCP). Thereby activating the transcription of YAP1 downstream target genes, which creates a positive feedback cycle to facilitate GC progression. Immunohistochemical analysis demonstrated significant upregulation of CPNE3 in GC tissues. Survival and Cox regression analyses indicated that high CPNE3 expression was an independent prognostic marker for GC. This study elucidated the pivotal involvement of an aberrantly activated CPNE3/YAP1 positive feedback loop in the malignant progression of GC, thereby uncovering novel prognostic factors and therapeutic targets in GC. [ABSTRACT FROM AUTHOR]

: Copyright of Cellular & Molecular Life Sciences is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

المؤلفون: Fan, Linwei, Li, Li, Huang, Chunye, Huang, Shanshan, Deng, Jun, Xiong, Jianping

المصدر: OncoTargets and Therapy ; volume Volume 13, page 10075-10085 ; ISSN 1178-6930

الإتاحة: https://doi.org/10.2147/ott.s262909Test
https://www.dovepress.com/getfile.php?fileID=62326Test

المؤلفون: Liu, Zhen, Li, Junhe, Ding, Yun, Ma, Mei, Chen, Jun, Lei, Wan, Li, Li, Yao, Yangyang, Yu, Xin, Zhong, Min, Liao, Quan, Fang, Weidan, Fan, Linwei, Huang, Chunye, Zhong, Hongguang, Wen, Qin, Fang, Zi, Chen, Jingyi, Huang, Shanshan, Xiong, Jianpin, Xiang, Xiaojun, Deng, Jun

المصدر: Oncogene ; volume 41, issue 18, page 2555-2570 ; ISSN 0950-9232 1476-5594

مصطلحات موضوعية: Cancer Research, Genetics, Molecular Biology

الإتاحة: https://doi.org/10.1038/s41388-022-02267-0Test
https://www.nature.com/articles/s41388-022-02267-0.pdfTest
https://www.nature.com/articles/s41388-022-02267-0Test