CTHRC1 promotes gastric cancer metastasis via HIF-1α/CXCR4 signaling pathway
CTHRC1 promotes gastric cancer metastasis via HIF-1α/CXCR4 signaling pathway
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CTHRC1通过HIF-1α/CXCR4信号通路促进胃癌转移
DOI：
10.1016/j.biopha.2019.109742
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发表时间：
2020-03-01
影响因子：
7.5
通讯作者：
Zang, Mingde
中科院分区：
文献类型：
--
作者：
Ding, Xusheng;Huang, Renhong;Zang, Mingde
转移是胃癌死亡的主要原因，其机制尚不清楚。胶原蛋白三螺旋重复序列1（collagen triple helix repeat containing 1，CTHRC 1）蛋白参与组织重塑过程，与实体瘤的发生和转移密切相关，但CTHRC 1在胃癌中的功能作用及其在肿瘤转移中的作用机制尚未完全阐明。在本研究中，根据TCGA和GEO数据库，CTHRC 1在肿瘤组织中高表达，并且与GC的不良预后相关。功能研究显示，CTHRC 1在GC中的过表达显著增加了细胞的迁移和侵袭能力。然而，CXCR 4沉默后，促进作用消失。此外，CTHRC 1通过上调HIF-1 α表达增加CXCR 4表达，这最终有助于促进细胞迁移和侵袭。抑制HIF-1 α表达可降低CXCR 4表达，并抑制胃癌细胞的迁移和侵袭。这些结果证实了我们的假设，即HIF-1 α/CXCR 4信号通路介导了CTHRC 1对胃癌细胞迁移和侵袭的促进作用。
Metastasis is the main cause of gastric cancer (GC) related death and the underlying mechanisms still remain unclear. Collagen triple helix repeat containing 1 (CTHRC1) protein is known to be involved in tissue remodeling processes and closely associated with carcinogenesis and metastasis in solid tumors, but the functional role of CTHRC1 and its underlying mechanism with tumor metastasis in GC have not been fully illuminated. In the present study, CTHRC1 was highly expressed in tumor tissues and associated with poor prognosis of GC according to TCGA and GEO database. Functional studies revealed that CTHRC1 overexpression in GC significantly increased cell migration and invasion capacity. However, the promoting effects were abolished subsequent to silencing of CXCR4. In addition, CTHRC1 increased CXCR4 expression through upregulating HIF-1 alpha expression, which eventually contributed to the promotion of cell migration and invasion. Inhibiting HIF-1 alpha expression decreased CXCR4 expression and suppressed cell migration and invasion in GC. These results substantiated our hypothesis that HIF-1 alpha/CXCR4 signaling pathway mediated the promoting effect of CTHRC1 on cell migration and invasion in GC.