ITGB1 Contributes to Matrix Stiffness–Induced Lipid Raft Organization and Promotes Hepatocellular Carcinoma Cell Migration
- 1Key Laboratory of Biorheological Science & Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing 400030, China
- 2School of Life Science, Southwest University, Chongqing 400715, China
Abstract
Matrix stiffening is a characteristic pathological feature of the hepatocellular carcinoma (HCC) microenvironment and promotes HCC cell migration. Lipid rafts are cholesterol–enriched plasma membrane microdomains involved in cell adhesion and migration. However, whether matrix stiffness promotes lipid raft organization and whether lipid rafts contribute to stiffness–promoted HCC cell migration remain unclear. Using two HCC cell lines cultured on polyacrylamide hydrogels with distinct stiffnesses, we found that stiff matrix enhanced cell migration, increased Area-normalized GM1 fluorescence, and upregulated Caveolin-1 and Flotillin-1 protein expression, consistent with enhanced lipid raft–associated membrane organization. Cholesterol depletion with methyl-β–cyclodextrin (MβCD) reduced GM1 fluorescence and attenuated migration on the Stiff matrix. Cholesterol replenishment partially restored GM1 fluorescence and wound closure after MβCD treatment. To explore how extracellular matrix stiffness is coupled to lipid raft organization, we next examined integrin β1 (ITGB1), a major extracellular matrix mechanoreceptor. The Stiff matrix increased ITGB1 protein expression, ITGB1–GM1 colocalization, and ITGB1 levels in raft-enriched fractions. ITGB1 knockdown reduced GM1 fluorescence, decreased Caveolin-1 and Flotillin-1 levels in raft-enriched fractions, and suppressed migration under Stiff–matrix conditions. These findings support a contributory role for ITGB1 in stiffness-associated lipid raft organization and HCC cell migration.
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BibTeX
@article{zhang2026itgb1,
title = {{ITGB1 Contributes to Matrix Stiffness–Induced Lipid Raft Organization and Promotes Hepatocellular Carcinoma Cell Migration}},
author = {Xu Zhang and Xinyu Liu and Yan Liu and Guanbin Song},
journal = {International Journal of Molecular Sciences},
year = {2026},
month = oct,
doi = {10.3390/ijms27219577},
url = {https://www.mdpi.com/1422-0067/27/21/9577},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - ITGB1 Contributes to Matrix Stiffness–Induced Lipid Raft Organization and Promotes Hepatocellular Carcinoma Cell Migration
AU - Xu Zhang
AU - Xinyu Liu
AU - Yan Liu
AU - Guanbin Song
PY - 2026
DA - 2026/10/26
JO - International Journal of Molecular Sciences
DO - 10.3390/ijms27219577
UR - https://www.mdpi.com/1422-0067/27/21/9577
AB - Matrix stiffening is a characteristic pathological feature of the hepatocellular carcinoma (HCC) microenvironment and promotes HCC cell migration. Lipid rafts are cholesterol–enriched plasma membrane microdomains involved in cell adhesion and migration. However, whether matrix stiffness promotes lipid raft organization and whether lipid rafts contribute to stiffness–promoted HCC cell migration remain unclear. Using two HCC cell lines cultured on polyacrylamide hydrogels with distinct stiffnesses, we found that stiff matrix enhanced cell migration, increased Area-normalized GM1 fluorescence, and upregulated Caveolin-1 and Flotillin-1 protein expression, consistent with enhanced lipid raft–associated membrane organization. Cholesterol depletion with methyl-β–cyclodextrin (MβCD) reduced GM1 fluorescence and attenuated migration on the Stiff matrix. Cholesterol replenishment partially restored GM1 fluorescence and wound closure after MβCD treatment. To explore how extracellular matrix stiffness is coupled to lipid raft organization, we next examined integrin β1 (ITGB1), a major extracellular matrix mechanoreceptor. The Stiff matrix increased ITGB1 protein expression, ITGB1–GM1 colocalization, and ITGB1 levels in raft-enriched fractions. ITGB1 knockdown reduced GM1 fluorescence, decreased Caveolin-1 and Flotillin-1 levels in raft-enriched fractions, and suppressed migration under Stiff–matrix conditions. These findings support a contributory role for ITGB1 in stiffness-associated lipid raft organization and HCC cell migration.
SN - 1422-0067
ER -