Galectin-1 induces hepatocellular carcinoma EMT and sorafenib resistance by activating FAK/PI3K/AKT signaling

P-F Zhang; K-S Li; Y-H Shen; P-T Gao; Z-R Dong; J-B Cai; C Zhang; X-Y Huang; M-X Tian; Z-Q Hu; D-M Gao; J Fan; A-W Ke; G-M Shi

doi:10.1038/cddis.2015.324

Galectin-1 induces hepatocellular carcinoma EMT and sorafenib resistance by activating FAK/PI3K/AKT signaling

Cell Death Dis. 2016 Apr 21;7(4):e2201. doi: 10.1038/cddis.2015.324.

Authors

P-F Zhang¹, K-S Li², Y-H Shen¹, P-T Gao¹, Z-R Dong¹, J-B Cai¹, C Zhang¹, X-Y Huang¹, M-X Tian¹, Z-Q Hu¹, D-M Gao¹, J Fan^{1

3}, A-W Ke¹, G-M Shi¹

Affiliations

¹ Key Laboratory of Carcinogenesis and Cancer Invasion, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Ministry of Education, Shanghai 200032, China.
² State Key Laboratory of Oncogenes & Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200032, China.
³ Cancer Center, Institutes of Biomedical Sciences, Fudan University, Shanghai 200031, China.

Abstract

Galectin-1 (Gal-1) is involved in several pathological activities associated with tumor progression and chemoresistance, however, the role and molecular mechanism of Gal-1 activity in hepatocellular carcinoma (HCC) epithelial-mesenchymal transition (EMT) and sorafenib resistance remain enigmatic. In the present study, forced Gal-1 expression promoted HCC progression and sorafenib resistance. Gal-1 elevated αvβ3-integrin expression, leading to AKT activation. Moreover, Gal-1 overexpression induced HCC cell EMT via PI3K/AKT cascade activation. Clinically, our data revealed that Gal-1 overexpression is correlated with poor HCC survival outcomes and sorafenib response. These data suggest that Gal-1 may be a potential therapeutic target for HCC and a biomarker for predicting response to sorafenib treatment.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Carcinoma, Hepatocellular / drug therapy
Carcinoma, Hepatocellular / mortality
Carcinoma, Hepatocellular / pathology
Cell Line, Tumor
Cell Proliferation / drug effects
Chromones / pharmacology
Drug Resistance, Neoplasm / drug effects
Epithelial-Mesenchymal Transition / drug effects*
Focal Adhesion Kinase 1 / metabolism*
Galectin 1 / antagonists & inhibitors
Galectin 1 / genetics
Galectin 1 / metabolism*
Humans
Integrin alphaVbeta3 / antagonists & inhibitors
Integrin alphaVbeta3 / genetics
Integrin alphaVbeta3 / metabolism
Liver Neoplasms / drug therapy
Liver Neoplasms / mortality
Liver Neoplasms / pathology
Male
Mice
Mice, Inbred C57BL
Mice, Nude
Morpholines / pharmacology
Neoplasm Invasiveness
Niacinamide / analogs & derivatives*
Niacinamide / pharmacology
Niacinamide / therapeutic use
Phenylurea Compounds / pharmacology*
Phenylurea Compounds / therapeutic use
Phosphatidylinositol 3-Kinases / metabolism*
Proto-Oncogene Proteins c-akt / antagonists & inhibitors
Proto-Oncogene Proteins c-akt / metabolism*
RNA Interference
Signal Transduction / drug effects
Sorafenib
Survival Rate

Substances

Chromones
Galectin 1
Integrin alphaVbeta3
Morpholines
Phenylurea Compounds
Niacinamide
2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
Sorafenib
Phosphatidylinositol 3-Kinases
Focal Adhesion Kinase 1
PTK2 protein, human
Proto-Oncogene Proteins c-akt