Academic Journal
Testis‐specific protein, Y‐linked 1 activates PI3K/ AKT and RAS signaling pathways through suppressing IGFBP3 expression during tumor progression
| العنوان: | Testis‐specific protein, Y‐linked 1 activates PI3K/ AKT and RAS signaling pathways through suppressing IGFBP3 expression during tumor progression |
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| المؤلفون: | Tu, Wenling, Yang, Bo, Leng, Xiangyou, Pei, Xue, Xu, Jinyan, Liu, Mohan, Dong, Qiang, Tao, Dachang, Lu, Yongjie, Liu, Yunqiang, Yang, Yuan |
| المساهمون: | National Natural Science Foundation of China |
| المصدر: | Cancer Science ; volume 110, issue 5, page 1573-1586 ; ISSN 1347-9032 1349-7006 |
| بيانات النشر: | Wiley |
| سنة النشر: | 2019 |
| المجموعة: | Wiley Online Library (Open Access Articles via Crossref) |
| الوصف: | The testis‐specific protein, Y‐linked 1 ( TSPY 1), a newly recognized cancer/testis antigen, has been suggested to accelerate tumor progression. However, the mechanisms underlying TSPY 1 cancer‐related function remain limited. By mining the RNA sequencing data of lung and liver tumors from The Cancer Genome Atlas, we found frequent ectopic expression of TSPY 1 in lung adenocarcinoma ( LUAD ) and liver hepatocellular carcinoma ( LIHC ), and the male‐specific protein was associated with higher mortality rate and worse overall survival in patients with LUAD and LIHC . Overexpression of TSPY 1 promotes cell proliferation, invasiveness, and cycle transition and inhibits apoptosis, whereas TSPY 1 knockdown has the opposite effects on these cancer cell phenotypes. Transcriptomic analysis revealed the involvement of TSPY 1 in PI 3K/ AKT and RAS signaling pathways in both LUAD and LIHC cells, which was further confirmed by the increase in the levels of phosphorylated proteins in the PI 3K‐ AKT and RAS signaling pathways in TSPY 1‐overexpressing cancer cells, and by the suppression on the activity of these two pathways in TSPY 1‐knockdown cells. Further investigation identified that TSPY 1 could directly bind to the promoter of insulin growth factor binding protein 3 ( IGFBP 3) to inhibit IGFBP 3 expression and that downregulation of IGFBP 3 increased the activity of PI 3K/ AKT / mTOR / BCL 2 and RAS / RAF / MEK / ERK / JUN signaling in LUAD and LIHC cells. Taken together, the observations reveal a novel mechanism by which TSPY 1 could contribute to the progression of LUAD and LIHC . Our finding is of importance for evaluating the potential of TSPY 1 in immunotherapy of male tumor patients with TSPY 1 expression. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| DOI: | 10.1111/cas.13984 |
| الاتاحة: | http://dx.doi.org/10.1111/cas.13984 https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1111%2Fcas.13984 https://onlinelibrary.wiley.com/doi/pdf/10.1111/cas.13984 https://onlinelibrary.wiley.com/doi/full-xml/10.1111/cas.13984 |
| Rights: | http://creativecommons.org/licenses/by-nc/4.0/ |
| رقم الانضمام: | edsbas.4651BDF2 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1111/cas.13984 |
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