RAB14 activates MAPK signaling to promote bladder tumorigenesis

Haichao Chao, Leihong Deng, Fanghua Xu, Bin Fu, Zunwei Zhu, Zhifeng Dong, Yen-Nien Liu, Tao Zeng

研究成果: 雜誌貢獻文章同行評審

20 引文 斯高帕斯(Scopus)

摘要

Bladder cancer (BC) is a fatal invasive malignancy accounting for approximately 5% of all cancer deaths in humans; however, the underlying molecular mechanisms and potential targeted therapeutics for BC patients remain unclear. We report herein that RAB14 was overexpressed in BC tissues and cells with high metastatic potential, and its abundance was significantly associated with lymph node metastasis (p=0.001), a high-grade tumor stage (p=0.009), poor differentiation (p<0.001), and unfavorable prognoses of BC patients (p=0.003, log-rank test). Interference by RAB14 mediated a reduction in the TWIST1 protein, and inhibited cell migration and invasion (p<0.05). Moreover, silencing RAB14 reduced cell proliferation and induced apoptosis in vitro and suppressed tumorigenesis in a mouse xenograft model. We demonstrated that RAB14-promoted BC cancer development and progression were associated with activation of mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) signaling through upregulation of MAPK1/MAPK8 and downregulation of DUSP6/SHC1/FOS. We provide evidence that RAB14 acts as a tumor promoter and modulates the invasion and metastatic potential of BC cells via activating the MAPK pathway.
原文英語
頁(從 - 到)1341-1351
頁數11
期刊Carcinogenesis
40
發行號11
早期上線日期2月 27 2019
DOIs
出版狀態已發佈 - 11月 25 2019

ASJC Scopus subject areas

  • 癌症研究

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