Suppression of Slit3 induces tumor proliferation and chemoresistance in hepatocellular carcinoma through activation of GSK3β/β-catenin pathway

BMC Cancer
Lui NgWai-Lun Law

Abstract

It is essential to understand the mechanisms responsible for hepatocellular carcinoma (HCC) progression and chemoresistance in order to identify prognostic biomarkers as well as potential therapeutic avenues. Recent findings have shown that SLIT3 appears to function as a novel tumor suppressor gene in various types of cancers, yet its clinical correlation and role in HCC has not been understood clearly. We determined the transcript levels of Slit3 in tumor and adjacent normal tissues within two cohorts (N = 40 and 25) of HCC patients, and correlated the gene expression with the clinicopathological data. Subsequently, the functional effects and underlying molecular mechanisms of Slit3 overexpression and/or repression were studied using cell-line and mouse models. Our results demonstrated a repression in Slit3 expression in nearly 50% of the HCC patients, while the overall expression of Slit3 inversely correlated with the size of the tumor in both cohorts of patients. Stable down-regulation of Slit3 in HCC cell-lines induced cell proliferation in vitro and tumor growth in vivo, while stable Slit3 overexpression repressed these effects. Molecular investigations showed that the stable Slit3 repression-induced cell proliferation was...Continue Reading

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Citations

Feb 23, 2019·Journal of Investigative Medicine : the Official Publication of the American Federation for Clinical Research·Yongning JiaJiafu Ji
Nov 23, 2019·Breast Cancer Research and Treatment·Ekaterina S KuliginaEvgeny N Imyanitov
Jun 14, 2020·Signal Transduction and Targeted Therapy·Weiwei TangXuehao Wang
Apr 2, 2021·The Journal of Surgical Research·Kathleen MarulandaSean E McLean
Apr 1, 2021·Genetics·Sivan YairGraham Coop

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Methods Mentioned

BETA
surgical resection
PCR
transfections
transfection

Software Mentioned

SigmaStat
ImageJ

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