PRELP reduce cell stiffness and adhesion to promote the growth and metastasis of colorectal cancer cells by binding to integrin α5

Exp Cell Res. 2024 Aug 1;441(1):114151. doi: 10.1016/j.yexcr.2024.114151. Epub 2024 Jul 9.

Abstract

PRELP is thought to be an inhibitor of the development and progression of a variety of malignancies. Metastasis is a major cause of death in patients with colorectal cancer, but the mechanism underlying the role of PRELP in colorectal cancer metastasis remains poorly understood. In this study, we found that PRELP was significantly higher in metastatic tissues than in non-metastatic tissues of colorectal cancer and was closely associated with poor prognosis of colorectal cancer patients. PRELP promotes growth and metastasis of colorectal cancer cells. PRELP reduces cell stiffness and adhesion. PRELP promoted EMT in colorectal cancer cells and that PRELP bind to integrin α5 to activate the integrin α5/FAK/AKT signaling pathway. In conclusion, we demonstrate that PRELP is upregulated in metastatic colorectal cancer, providing a potential prognostic marker and therapeutic target for the clinical management of metastatic colorectal cancer from a biomechanical perspective.

Keywords: Colorectal cancer; EMT; Integrin α5; PRELP; Stiffness and adhesion.

MeSH terms

  • Animals
  • Cell Adhesion*
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation*
  • Colorectal Neoplasms* / genetics
  • Colorectal Neoplasms* / metabolism
  • Colorectal Neoplasms* / pathology
  • Epithelial-Mesenchymal Transition
  • Extracellular Matrix Proteins* / genetics
  • Extracellular Matrix Proteins* / metabolism
  • Female
  • Gene Expression Regulation, Neoplastic
  • Glycoproteins* / genetics
  • Glycoproteins* / metabolism
  • Humans
  • Integrin alpha5* / genetics
  • Integrin alpha5* / metabolism
  • Integrins
  • Male
  • Mice
  • Mice, Nude
  • Neoplasm Metastasis
  • Prognosis
  • Proto-Oncogene Proteins c-akt / metabolism
  • Signal Transduction

Substances

  • Integrin alpha5
  • Integrins
  • ITGA5 protein, human
  • Proto-Oncogene Proteins c-akt
  • PRELP protein, human
  • Glycoproteins
  • Extracellular Matrix Proteins