Cirrhotic stiffness affects the migration of hepatocellular carcinoma cells and induces sorafenib resistance through YAP

Journal of Cellular Physiology
Jian GaoCongying Wu

Abstract

A majority of hepatocellular carcinomas (HCCs) combine with liver cirrhosis. The cirrhotic liver has been implicated in interfering with the effects of HCC-targeted drugs, including sorafenib. Alterations in the tumor microenvironment of the cirrhotic liver include both biochemical and biomechanical factors. In this study, we induced sorafenib resistance in HCC cells. We observed changes in cell morphology, cytoskeletal architecture, and cellular stiffness in these sorafenib-resistant cells, resembling those adapted to stiffer substrates. To examine the contribution of mechanical factors in HCC cell growth and drug resistance, we used an in vitro cell culture system with adjustable stiffness mimicking the normal or cirrhotic liver tissues. We identified that mechanical adaptation conferred HCC cells with increased motility and sorafenib resistance. We further reported the mechanism underlying the involvement of the transcription coactivator YAP. Our results underline the important role of mechanical factors in the interaction between tumor cells and their microenvironment.

References

Sep 20, 2005·Cancer Cell·Matthew J PaszekValerie M Weaver
Apr 12, 2006·Nature Reviews. Molecular Cell Biology·Viola Vogel, Michael Sheetz
Apr 16, 2008·Journal of Gastroenterology and Hepatology·Kwang-Hyub Han, Jun Yong Park
Oct 18, 2008·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·John A ContiJohn P Iredale
Dec 5, 2008·The New England Journal of Medicine·Giancarlo Spinzi, Silvia Paggi
Feb 7, 2009·Nature Reviews. Molecular Cell Biology·Diana E Jaalouk, Jan Lammerding
Jul 8, 2009·Biophysical Journal·Vikash P ChauhanRakesh K Jain
Nov 26, 2009·Cell·Kandice R LeventalValerie M Weaver
Jan 30, 2010·Nature·Daniel A Fletcher, R Dyche Mullins
Mar 10, 2011·Nature Reviews. Clinical Oncology·Andrew X ZhuRakesh K Jain
Apr 22, 2011·Nature Reviews. Molecular Cell Biology·Christopher C DuFortValerie M Weaver
May 24, 2011·Journal of Cellular Physiology·Joan FernandoIsabel Fabregat
Jun 10, 2011·Nature·Sirio DupontStefano Piccolo
Jun 27, 2012·EMBO Molecular Medicine·Nicholas A SaundersAlexander Guminski
Aug 31, 2012·Biochemistry·Elizabeth C LesseyKeith Burridge
Jan 15, 2013·Gastroenterology·Virginia Hernandez-GeaJosep M Llovet
Jan 3, 2014·Physiological Reviews·Laurent BlanchoinJulie Plastino
Jun 10, 2014·Journal of Cellular Physiology·Hossein A HamedPaul Dent
Sep 16, 2014·International Journal of Cancer. Journal International Du Cancer·Jacques FerlayFreddie Bray
Apr 24, 2015·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Jessica LoTerence Kin Wah Lee
Jul 24, 2015·Nature Protocols·Thomas ReibergerDan G Duda
Oct 4, 2015·The Journal of Biological Chemistry·Megan L Finch-EdmondsonBernard A Callus
Jan 13, 2016·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Seema S DesaiTammy T Chang
Jun 15, 2016·Annual Review of Cell and Developmental Biology·Laralynne PrzybylaValerie M Weaver
Jun 15, 2016·Cancer Cell·Francesca ZanconatoStefano Piccolo
Mar 28, 2017·Acta Pharmacologica Sinica·Yan-Jing ZhuLei Chen
May 26, 2017·Cell Reports·Yiting QiaoMarius Sudol

❮ Previous
Next ❯

Citations

Jun 27, 2020·Cancers·Jose J G MarinOscar Briz
Jan 14, 2020·Biochimica Et Biophysica Acta. Reviews on Cancer·Francesca ReggianiValentina Sancisi
Jan 23, 2022·Nature Reviews. Gastroenterology & Hepatology·Jacquelyn O Russell, Fernando D Camargo

❮ Previous
Next ❯

Related Concepts

Related Feeds

Carcinoma, Hepatocellular

Hepatocellular Carcinoma is a malignant cancer in liver epithelial cells. Discover the latest research on Hepatocellular Carcinoma here.

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.

Related Papers

Clinical Advances in Hematology & Oncology : H&O
Pierre Gholam
Liver International : Official Journal of the International Association for the Study of the Liver
Giovanni B Levi SandriPasquale B Berloco
© 2022 Meta ULC. All rights reserved