Research Paper Volume 13, Issue 14 pp 19064—19076

Type I collagen promotes tumor progression of integrin β1 positive gastric cancer through a BCL9L/β-catenin signaling pathway

Yalei Lv1, , Yujie Shan1, , Lina Song2, , Yufei Zhao3, , Ruixue Lai3, , Junyan Su4, , Xiaoyun Zhang3, ,

  • 1 Department of Medical Oncology, The Fourth Hospital of Hebei Medical University, Hebei, China
  • 2 Department of Oncology, Cangzhou Central Hospital, Hebei, China
  • 3 Department of Immunology and Rheumatology, The Fourth Hospital of Hebei Medical University, Hebei, China
  • 4 Lifehealthcare Clinical Laboratories, Hangzhou, Zhejiang, China

Received: January 1, 2021       Accepted: June 5, 2021       Published: July 28, 2021
How to Cite

Copyright: © 2021 Lv et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


The mechanism of extracellular matrix induced tumor progression is poorly understood. Based on the TCGA database and clinical tumor tissues analysis, we observed abundant type I collagen expression in tumor tissues and poor overall survival in gastric patients with high integrin β1 (ITGB1) expression. In vitro, our study found that 3D collagen culture promoted the capability of colony formation and growth in ITGB1 positive gastric cancer, whereas limited colony growth was observed in ITGB1 negative gastric cancer, suggesting the role of ITGB1 in type I collagen associated tumor progression. Mechanistically, we demonstrated that type I collagen was capable of promoting the activation of BCL9L/β-catenin signaling pathway through ITGB1, thereby contributing to the gastric cancer development. Subsequently, β-catenin signals further up-regulated the expression anti-apoptosis protein BCL2, leading to the chemo-resistance in gastric cancer cells. Blockade of β-catenin signals efficiently improved the anticancer effects of chemotherapy, providing an innovative sight for clinical gastric cancer therapy.


ITGB1: integrin β1; CR: chemo-resistant; CS: chemo-sensitive; C-IN2: β-catenin inhibitor β-catenin-IN2.