Department of Gastroenterology, Xi'an Central Hospital, Xi'an, Shaanxi, China.
J Cell Physiol. 2020 Mar;235(3):2071-2079. doi: 10.1002/jcp.29107. Epub 2019 Jul 25.
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.
人类染色体分离 1 样（CSE1L）基因作为细胞增殖、侵袭和凋亡的关键分子介质在细胞中发挥作用。CSE1L 与多种人类癌症的肿瘤进展有关。更深入地了解 CSE1L 的分子机制有助于癌症治疗。在本研究中，我们表明 CSE1L 在胃癌（GC）细胞系中高表达。CSE1L 沉默促进细胞凋亡，抑制细胞增殖和侵袭。糖蛋白非转移性黑色素瘤蛋白 B（GPNMB）的过表达逆转了 CSE1L 抑制的抗癌作用。CSE1L 抑制通过小眼畸形相关转录因子（MITF）降低 GPNMB。此外，GPNMB 调节磷酸肌醇 3-激酶（PI3K）/蛋白激酶 B（Akt）/雷帕霉素靶蛋白（mTOR）和丝裂原活化蛋白激酶激酶（MEK）/细胞外信号调节激酶（ERK）信号通路。综上所述，我们的研究表明，CSE1L 抑制降低了 MITF 并抑制了 GPNMB 的表达，从而激活了 PI3K/Akt/mTOR 和 MEK/ERK 信号通路，最终抑制了 GC 中的肿瘤生长和转移。
