SPHK1 (sphingosine kinase 1) induces epithelial-mesenchymal transition by promoting the autophagy-linked lysosomal degradation of CDH1/E-cadherin in hepatoma cells

Autophagy
Hong LiuRong-Guang Shao

Abstract

SPHK1 (sphingosine kinase 1), a regulator of sphingolipid metabolites, plays a causal role in the development of hepatocellular carcinoma (HCC) through augmenting HCC invasion and metastasis. However, the mechanism by which SPHK1 signaling promotes invasion and metastasis in HCC remains to be clarified. Here, we reported that SPHK1 induced the epithelial-mesenchymal transition (EMT) by accelerating CDH1/E-cadherin lysosomal degradation and facilitating the invasion and metastasis of HepG2 cells. Initially, we found that SPHK1 promoted cell migration and invasion and induced the EMT process through decreasing the expression of CDH1, which is an epithelial marker. Furthermore, SPHK1 accelerated the lysosomal degradation of CDH1 to induce EMT, which depended on TRAF2 (TNF receptor associated factor 2)-mediated macroautophagy/autophagy activation. In addition, the inhibition of autophagy recovered CDH1 expression and reduced cell migration and invasion through delaying the degradation of CDH1 in SPHK1-overexpressing cells. Moreover, the overexpression of SPHK1 produced intracellular sphingosine-1-phosphate (S1P). In response to S1P stimulation, TRAF2 bound to BECN1/Beclin 1 and catalyzed the lysine 63-linked ubiquitination of BECN1...Continue Reading

References

Jan 18, 2006·The Journal of Biological Chemistry·Grégory LavieuPatrice Codogno
Oct 24, 2007·Experimental Cell Research·Carla CicchiniMarco Tripodi
Nov 17, 2007·Genes & Development·Noboru Mizushima
Mar 6, 2008·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Emilia FransveaGianluigi Giannelli
May 17, 2008·Cancer Research·Tamer T OnderRobert A Weinberg
Oct 7, 2008·World Journal of Gastroenterology : WJG·Bo ZhaiHong-Yang Wang
May 4, 2011·World Journal of Biological Chemistry·Yuan-Li HuangHsinyu Lee
Jun 15, 2011·Radiotherapy and Oncology : Journal of the European Society for Therapeutic Radiology and Oncology·Carmen HolzIngeborg Tinhofer
Jul 13, 2011·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Tao SunZhi-yong Liu
Aug 16, 2011·The Journal of Immunology : Official Journal of the American Association of Immunologists·Su MiZhuo-Wei Hu
Nov 22, 2011·Liver International : Official Journal of the International Association for the Study of the Liver·Meiyan BaoXianghuo He
Aug 4, 2012·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Heng LinZhuo-Wei Hu
Nov 14, 2012·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·Christopher A LambSharon A Tooze
Apr 3, 2013·Biochemical and Biophysical Research Communications·Caixia ZhangRongguang Shao
Aug 27, 2013·The EMBO Journal·Pengyan XiaZusen Fan
Mar 29, 2014·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Bryan C FuchsKenneth K Tanabe
Dec 30, 2014·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Zijie ZhangChunyang Mai
May 30, 2015·Molecular Oncology·Myriam CatalanoSabrina Di Bartolomeo

❮ Previous
Next ❯

Citations

Dec 5, 2018·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Tiantian YanYuesheng Huang
Apr 23, 2019·International Journal of Hyperthermia : the Official Journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group·Jiayun JiangKuansheng Ma
Mar 8, 2019·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Wei WangDeron R Herr
Jul 6, 2019·Cell Adhesion & Migration·Zhujun ChengTianyu Han
Jul 23, 2020·American Journal of Physiology. Lung Cellular and Molecular Physiology·Alison W HaAnantha Harijith
Apr 28, 2019·International Journal of Molecular Sciences·Hyunkoo KangBuHyun Youn
May 29, 2018·Experimental and Therapeutic Medicine·Zhijing ZhaoShushu Wang
Aug 30, 2020·Cells·Lorry CarriéNathalie Andrieu-Abadie
Jul 28, 2020·Frontiers in Cell and Developmental Biology·Valentina DamianoManuela Santarosa
Apr 5, 2020·International Journal of Molecular Sciences·Katja JakobiGeorgios Grammatikos
Dec 16, 2020·Cancer Control : Journal of the Moffitt Cancer Center·Xianwang WangYingying Lu
Jan 8, 2021·Frontiers in Cell and Developmental Biology·Jacopo Di GregorioVincenzo Flati
Dec 10, 2020·Cell & Bioscience·Tao TangShi-Cang Yu
Feb 12, 2021·Cellular Signalling·MelissaR PitmanStuart M Pitson
Mar 2, 2021·Frontiers in Medicine·Miaomiao ZhaoZhenggang Yang
Oct 24, 2020·Clinica Chimica Acta; International Journal of Clinical Chemistry·Zhiyang Chen, Min Hu
Jul 19, 2021·Biochimica Et Biophysica Acta. Reviews on Cancer·Yuanyang WangWeibin Wang
Sep 24, 2021·Gastric Cancer : Official Journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association·Iori MotooIchiro Yasuda

❮ Previous
Next ❯

Methods Mentioned

BETA
electron microscopy
confocal microscopy
ubiquitination
transfection
co-immunoprecipitation
immunoprecipitation

Software Mentioned

ImageJ
SPSS
Leica confocal

Related Concepts

Related Feeds

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.

Autophagy & Model Organisms

Autophagy is a cellular process that allows degradation by the lysosome of cytoplasmic components such as proteins or organelles. Here is the latest research on autophagy & model organisms

Cell Migration

Cell migration is involved in a variety of physiological and pathological processes such as embryonic development, cancer metastasis, blood vessel formation and remoulding, tissue regeneration, immune surveillance and inflammation. Here is the latest research.

Cell Migration in Cancer and Metastasis

Migration of cancer cells into surrounding tissue and the vasculature is an initial step in tumor metastasis. Discover the latest research on cell migration in cancer and metastasis here.

Autophagy & Aging: Inhibitors

The feed focuses on the role of nuclear export inhibitors and their effect on autophagy and the aging process.