2. Academic Validation
  3. Matrix metalloproteinase-2 inducing COL1A1 synthesis via integrin alpha Ⅴ promotes invasion and metastasis of cholangiocarcinoma cells

Matrix metalloproteinase-2 inducing COL1A1 synthesis via integrin alpha Ⅴ promotes invasion and metastasis of cholangiocarcinoma cells

  • Ann Hepatol. 2023 Dec 18:101279. doi: 10.1016/j.aohep.2023.101279.
Shuguang Pan 1,  Ying Hu 2,  Lang Gan 1,  Jiejuan Lai 1,  Ping Zheng 1,  YuJun Zhang 1,  Ling Shuai 1,  Yan Jiang 1,  Mo Chen 3,  Junping Wang 4,  Yu He 1
Affiliations

Affiliations

  • 1 Institute of Hepatobiliary Surgery, Southwest Hospital, Third Military Medical University, 30 Gaotanyan Street, Chongqing 400038, China.
  • 2 Oncology Department, Southwest Hospital, Third Military Medical University, 30 Gaotanyan Street, Chongqing 400038, China.
  • 3 State Key Laboratory of Trauma, Burns and Combined Injury, Institute of Combined Injury, College of Preventive Medicine, Third Military Medical University, 30 Gaotanyan Street, Chongqing 400038, China.
  • 4 State Key Laboratory of Trauma, Burns and Combined Injury, Institute of Combined Injury, College of Preventive Medicine, Third Military Medical University, 30 Gaotanyan Street, Chongqing 400038, China. Electronic address: [email protected].
PMID: 38123132 DOI: 10.1016/j.aohep.2023.101279
Abstract

Introduction and objectives: Cholangiocarcinoma (CCA) is characterized by early distant invasion and metastasis, whereas the underlying mechanism is still obscure. Increasing evidence shows that collagen type Ι alpha 1 (COL1A1) is a gene associated with the progression of multiple diseases. Here, we attempted to investigate the role of COL1A1 in CCA.

Materials and methods: The expression of COL1A1 between tumor tissues and adjacent normal tissues obtained from CCA patients was detected by Western blot and immunofluorescence, followed by analysis of its clinical significance. Then, the biological effects of COL1A1 overexpression or knockdown on CCA cells were evaluated in vitro and in vivo. Finally, molecular mechanism of COL1A1 in regulating the invasion and metastasis of CCA cells was determined by a series of experiments.

Results: COL1A1 expression was significantly higher in CCA pathological tissues than in corresponding adjacent normal tissues. Analysis of 83 CCA patients showed that higher expression of COL1A1 was correlated with poorer patient prognosis. Notably, overexpression or knockdown experiments revealed that COL1A1 contributed to the migration and invasion, as well as epithelial-to-mesenchymal transition (EMT), in CCA cells. Further investigations demonstrated that matrix metalloproteinase-2 (MMP2) promoted COL1A1 upregulation via the Integrin alpha Ⅴ pathway, therefore affecting ECM remodelling and inducing EMT in CCA cells. Moreover, COL1A1 expression was positively related to PD-1 and PD-L1 in CCA, and COL1A1 increased PD-L1 expression by activating the NF-κB pathway.

Conclusions: COL1A1 plays an important role in regulating CCA progression and may act as a promising biomarker and therapeutic target for CCA.

Keywords

COL1A1; Cholangiocarcinoma; Integrin alpha Ⅴ; MMP2; Metastasis.

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