2. Academic Validation
  3. CTHRC1 promotes gastric cancer metastasis via HIF-1α/CXCR4 signaling pathway

CTHRC1 promotes gastric cancer metastasis via HIF-1α/CXCR4 signaling pathway

  • Biomed Pharmacother. 2020 Mar;123:109742. doi: 10.1016/j.biopha.2019.109742.
Xusheng Ding 1,  Renhong Huang 2,  Yiming Zhong 3,  Na Cui 4,  Yifei Wang 5,  Junyong Weng 6,  Li Chen 6,  Mingde Zang 7
Affiliations

Affiliations

  • 1 Department of Gastric Cancer Surgery, Fudan University, Shanghai Cancer Center, Shanghai 200032, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China; Department of General Surgery of Changzheng Hospital Affiliated to Naval Military Medical University, Fengyang Road, Shanghai, 200003, China; Department of Surgery, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Ruijin Er Road, Shanghai 200025, China.
  • 2 Department of General Surgery of Changzheng Hospital Affiliated to Naval Military Medical University, Fengyang Road, Shanghai, 200003, China.
  • 3 Department of General Surgery of Changzheng Hospital Affiliated to Naval Military Medical University, Fengyang Road, Shanghai, 200003, China; Department of Surgery, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Ruijin Er Road, Shanghai 200025, China.
  • 4 Department of Pathology of Changzheng Hospital Affiliated to Naval Military Medical University, Fengyang Road, Shanghai, 200003, China.
  • 5 Department of Cardiothoracic Surgery of Changzheng Hospital Affiliated to Naval Military Medical University, Fengyang Road, Shanghai, 200003, China.
  • 6 Department of Gastric Cancer Surgery, Fudan University, Shanghai Cancer Center, Shanghai 200032, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China.
  • 7 Department of Gastric Cancer Surgery, Fudan University, Shanghai Cancer Center, Shanghai 200032, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China; Department of Surgery, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Ruijin Er Road, Shanghai 200025, China. Electronic address: zmd8910@163.com.
PMID: 31855733 DOI: 10.1016/j.biopha.2019.109742
Abstract

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-1α expression, which eventually contributed to the promotion of cell migration and invasion. Inhibiting HIF-1α expression decreased CXCR4 expression and suppressed cell migration and invasion in GC. These results substantiated our hypothesis that HIF-1α/CXCR4 signaling pathway mediated the promoting effect of CTHRC1 on cell migration and invasion in GC.

Keywords

CTHRC1; CXCR4; Gastric cancer; HIF-1α; Metastasis.

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