The role of XBP1s in the metastasis and prognosis of hepatocellular carcinoma

Autor: Jingbo Kang, Chen Gao, Tao Sun, Juyi Wen, Sudong Wu, Rui Du
Rok vydání: 2018
Předmět:
0301 basic medicine
Male
X-Box Binding Protein 1
Carcinoma
Hepatocellular
Epithelial-Mesenchymal Transition
Biophysics
Mice
Nude
Snail
Biochemistry
Metastasis
03 medical and health sciences
0302 clinical medicine
biology.animal
Cell Line
Tumor
Medicine
Animals
Humans
Neoplasm Invasiveness
Epithelial–mesenchymal transition
Neoplasm Metastasis
neoplasms
Molecular Biology
Mice
Inbred BALB C
biology
business.industry
Endoplasmic reticulum
Liver Neoplasms
Twist-Related Protein 1
Cell migration
Cell Biology
Middle Aged
medicine.disease
Cadherins
Prognosis
digestive system diseases
In vitro
Gene Expression Regulation
Neoplastic
Alternative Splicing
030104 developmental biology
Cell culture
030220 oncology & carcinogenesis
Hepatocellular carcinoma
Cancer research
Female
Snail Family Transcription Factors
business
Zdroj: Biochemical and biophysical research communications. 500(3)
ISSN: 1090-2104
Popis: Tumor metastasis and recurrence are the primary contributors to poor prognosis in patients with hepatocellular carcinoma (HCC). The epithelial-mesenchymal transition (EMT) of tumor cells is the predominant mechanism of HCC progression. XBP1s is a newly discovered molecule involved in the endoplasmic reticulum (ER) stressresponse, which is an adaptive response and defense mechanism in cells that enablessurvival under adverse conditions. Abnormally high XBP1sexpression has been found in tumor cells, but the role of XBP1sin HCC progression remains unclear. We found that the expression of XBP1s in HCC cell lines and tissuesamples was higher than that in control cells and tissuesamples. Clinicopathological analysis showed that the expression of XBP1s was closely correlated with distant metastasis and poor prognosis in HCC. In vivo and invitro experiments confirmed that the overexpression of XBP1s promoted EMT and metastasis in HCC cells. XBP1ssilencing attenuated cellular migration and development of the EMT phenotypein vitro. Through further study to elucidate the molecular mechanism underlying the promotion ofEMT by XBP1s in HCC cells, we confirmed that XBP1s could mediate the expression of Twist. In HCC cells, XBP1s enhanced the expression of Twist and Snail, resulting in a subsequent reduction in the expression of E-cadherin, a contributor to cell-cell adhesion. Overall, this study reveals a novel XBP1s/Twist/Snail axis that mediates EMT in HCC cells and the invasion and metastasis of HCC.
Databáze: OpenAIRE
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