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CSE1L silence inhibits the growth and metastasis in gastric cancer by repressing GPNMB via positively regulating transcription factor MITF
Author(s) -
Li Yijun,
Yuan Shanshan,
Liu Jiaming,
Wang Yu,
Zhang Yanting,
Chen Xiaolu,
Si Wangli
Publication year - 2020
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.29107
Subject(s) - microphthalmia associated transcription factor , pi3k/akt/mtor pathway , cancer research , mapk/erk pathway , protein kinase b , protein kinase a , kinase , microbiology and biotechnology , signal transduction , medicine , biology , transcription factor , biochemistry , gene
Abstract Human chromosomal segregation 1‐like (CSE1L) gene functions as a key molecular mediator in cellular proliferation, invasion, and apoptosis. The association of CSE1L with tumor progression has been reported in diverse human cancers. A greater understanding of CSE1L molecular mechanism is beneficial for cancer treatment. In the current study, we show that CSE1L was highly expressed in gastric cancer (GC) cell lines. CSE1L silence promoted apoptosis and inhibited cell proliferation and invasion. Overexpression of glycoprotein nonmetastatic melanoma protein B (GPNMB) reversed the anticancer effect of CSE1L inhibition. CSE1L inhibition decreased GPNMB by microphthalmia‐associated transcription factor (MITF). Moreover, GPNMB regulates the phosphoinositide 3‐kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) and mitogen‐activated protein kinase kinase (MEK)/extracellular signal‐regulated kinase (ERK) signaling pathway. Taken together, our study revealed that CSE1L inhibition decreased MITF and suppressed GPNMB expression, thereby activating the PI3K/Akt/mTOR and MEK/ERK signaling pathway, ultimately inhibiting the tumor growth and metastasis in GC.