Silencing of lemur tyrosine kinase 2 restricts the proliferation and invasion of hepatocellular carcinoma through modulation of GSK-3β/Wnt/β-catenin signaling

Biochemical and Biophysical Research Communications
Gang ZhaoJinhai Wang

Abstract

Lemur tyrosine kinase 2 (LMTK2) was recently identified as a novel cancer-related gene in several human cancers. However, little is known of its function in hepatocellular carcinoma (HCC). Here we aim to investigate the expression pattern, biological function, and regulatory mechanism of LMTK2 in HCC. We found that LMTK2 was highly expressed in HCC tissues, and patients with high expression of LMTK2 in tumor tissues had shorter survival times. LMTK2 expression was also elevated in HCC cell lines, and LMTK2 silencing markedly repressed the proliferation and invasion of HCC cells. By contrast, LMTK2 overexpression exerted promotion effects on HCC cell proliferation and invasion. Our results demonstrate that LMTK2 silencing decreases the phosphorylation of glycogen synthase kinase-3β (GSK-3β) and the expression of an active β-catenin protein, leading to inhibition of Wnt/β-catenin signaling. Notably, GSK-3β inhibition significantly reversed the LMTK2 silencing-mediated antitumor effect on proliferation, invasion, and Wnt/β-catenin signaling in HCC cells. LMTK2 silencing retarded the tumor growth of HCC cells in an in vivo xenograft tumor model, associated with downregulation of Wnt/β-catenin signaling. In conclusion, our findings ...Continue Reading

References

Sep 16, 1998·Proceedings of the National Academy of Sciences of the United States of America·M DelcommenneS Dedhar
Apr 3, 2001·Genetics in Medicine : Official Journal of the American College of Medical Genetics·W W Grody, R J Desnick
Oct 24, 2002·The Journal of Biological Chemistry·Hong Wang, David L Brautigan
Mar 10, 2004·Genes to Cells : Devoted to Molecular & Cellular Mechanisms·Seiji KawaTadashi Yamamoto
Apr 15, 2005·Nature·Tannishtha Reya, Hans Clevers
Dec 13, 2006·Proceedings of the National Academy of Sciences of the United States of America·Seiji KawaTadashi Yamamoto
Jun 29, 2007·Nature Clinical Practice. Oncology·Myron SchwartzManousos Konstadoulakis
Feb 12, 2008·Nature Genetics·Rosalind A EelesDouglas F Easton
Apr 24, 2008·Genes to Cells : Devoted to Molecular & Cellular Mechanisms·Takeshi InoueKazuo Sutoh
Jan 10, 2012·Journal of Neurochemistry·Catherine ManserChristopher C J Miller
Jun 12, 2012·Cell·Hans Clevers, Roel Nusse
Sep 15, 2012·Genome Research·Jeong-Sun SeoYoung Tae Kim
Nov 2, 2012·American Journal of Physiology. Cell Physiology·Alexander NixonNeil A Bradbury
Apr 15, 2014·The Journal of Biological Chemistry·Simão LuzAgnieszka Swiatecka-Urban
May 27, 2015·Oncotarget·Kalpit Shah, Neil A Bradbury
Jul 29, 2015·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Xuewen LiuAlain C Borczuk
Aug 19, 2015·Clinical Gastroenterology and Hepatology : the Official Clinical Practice Journal of the American Gastroenterological Association·Amit G Singal, Hashem B El-Serag
Jan 27, 2016·World Journal of Gastroenterology : WJG·Valery VilchezRoberto Gedaly
Apr 11, 2018·Molecular Brain·János BenczeTibor Hortobágyi
Jan 9, 2019·CA: a Cancer Journal for Clinicians·Rebecca L SiegelAhmedin Jemal
Feb 15, 2019·Frontiers in Pharmacology·Daniel F CruzAgnieszka Swiatecka-Urban

❮ Previous
Next ❯

Citations

Jun 3, 2021·International Journal of Molecular Sciences·Elena FerrariSaverio Bettuzzi
May 18, 2020·Biochimica Et Biophysica Acta. Molecular Cell Research·Maria R EmmaMelchiorre Cervello

❮ Previous
Next ❯

Related Concepts

Related Feeds

Adherens Junctions

An adherens junction is defined as a cell junction whose cytoplasmic face is linked to the actin cytoskeleton. They can appear as bands encircling the cell (zonula adherens) or as spots of attachment to the extracellular matrix (adhesion plaques). Adherens junctions uniquely disassemble in uterine epithelial cells to allow the blastocyst to penetrate between epithelial cells. Discover the latest research on adherens junctions here.

Cadherins and Catenins

Cadherins (named for "calcium-dependent adhesion") are a type of cell adhesion molecule (CAM) that is important in the formation of adherens junctions to bind cells with each other. Catenins are a family of proteins found in complexes with cadherin cell adhesion molecules of animal cells: alpha-catenin can bind to β-catenin and can also bind actin. β-catenin binds the cytoplasmic domain of some cadherins. Discover the latest research on cadherins and catenins here.