Oncogenic role of mortalin contributes to ovarian tumorigenesis by activating the MAPK-ERK pathway.
Oncogenic role of mortalin contributes to ovarian tumorigenesis by activating the MAPK-ERK pathway.
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Mortalin 的致癌作用通过激活 MAPK-ERK 通路促进卵巢肿瘤发生
DOI：
10.1111/jcmm.12905
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发表时间：
2016-11
影响因子：
5.3
通讯作者：
Zuo J
中科院分区：
文献类型：
--
作者：
Hu Y;Yang L;Yang Y;Han Y;Wang Y;Liu W;Zuo J
Mortalin在人类恶性肿瘤中经常过度表达。以前的研究表明，mortalin有助于卵巢癌的发生和发展，但还需要进一步的研究。本研究的目的是阐明mortalin在卵巢癌发生发展中的作用机制。本研究利用慢病毒携带的mortalin短发夹状RNA(ShRNA)在A2780和A2780/cis卵巢癌细胞系中敲除mortalin的表达，并用慢病毒mortalin-pLVX-AcGFP构建过表达mortalin的细胞系。细胞计数Kit-8实验、集落形成实验、创伤愈合实验和Transwell细胞侵袭实验表明，mortalin表达降低分别抑制了卵巢癌细胞的增殖、集落形成、迁移和侵袭。流式细胞术结果表明，mortalin促进了G1期的转变，导致更快地恢复正常的细胞周期分布。Mortalin下调后，C-myc和Cyclin-D1等细胞周期蛋白显著增加，Cyclin-B1显著降低。Western印迹分析显示，mortalin基因敲除可显著降低p-c-Raf和p-ERK1/2通路，但不影响Jun氨基末端激酶通路，而mortalin过表达则有相反作用。综上所述，这些结果表明mortalin是一个致癌因子，mortalin激活的丝裂原活化蛋白激酶-ERK信号通路可能在卵巢癌的发生发展中起作用。
Mortalin is frequently overexpressed in human malignancies. Previous studies have suggested that mortalin contributes to ovarian cancer development and progression, but further investigation is warranted. The aim of this study is to elucidate the mechanism of mortalin in ovarian cancer development and progression. In this study, lentivirus‐delivered mortalin short hairpin RNA (shRNA) was used to knockdown mortalin expression in A2780 and A2780/cis ovarian cancer cell lines, and lentiviral mortalin‐pLVX‐AcGFP was used to generate mortalin‐overexpressing cell lines. The results demonstrated that decreased mortalin expression reduced ovarian cancer cell proliferation, colony formation, migration and invasion by Cell Counting Kit‐8 assay, colony formation assay, wounding healing assay and Transwell cell invasion assay, respectively. Flow cytometry results suggested that mortalin promotes the G1 transition, leading to faster restoration of a normal cell‐cycle distribution. Cell‐cycle proteins, including C‐myc and Cyclin‐D1, significantly increased, and Cyclin‐B1 remarkably decreased upon mortalin down‐regulation. Western blot analysis showed that mortalin knockdown significantly decreased p‐c‐Raf and phospho‐extracellular–regulated protein kinases (p‐ERK1/2) pathways but not the Jun N‐terminal kinase pathway, whereas mortalin overexpression had the opposite effect. Taken together, these results indicate that mortalin is an oncogenic factor, and mitogen‐activated protein kinase‐ERK signalling pathway activation by mortalin may contribute to ovarian cancer development and progression.
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DOI：
10.1038/nrc2644
发表时间：
2009-06
期刊：
Nature reviews. Cancer
影响因子：
--
作者：
通讯作者：
--
影响因子：
4.8
作者：
Kaul, SC;Aida, S;Wadhwa, R
通讯作者：
Wadhwa, R
DOI：
10.1016/j.bbrc.2011.05.116
发表时间：
2011-06-24
影响因子：
3.1
作者：
Yang, Hui;Zhou, Xiaoping;Liu, Wen
通讯作者：
Liu, Wen
影响因子：
--
作者：
Karst AM;Drapkin R
通讯作者：
Drapkin R
DOI：
10.1146/annurev.pathol.4.110807.092246
发表时间：
2009
期刊：
Annual review of pathology
影响因子：
--
作者：
Cho KR;Shih IeM
通讯作者：
Shih IeM