BTG2 suppresses cancer cell migration through inhibition of Src-FAK signaling by downregulation of reactive oxygen species generation in mitochondria.

Clinical & Experimental Metastasis
Seo-Kyung LimTae Jun Park

Abstract

BTG2 is a tumor suppressor gene. It is frequently downregulated in human cancer tissues, and its loss is associated with cancer cell metastasis, suggesting that the suppression of BTG2 plays a critical role in cancer cell migration and invasion. Here, we report that re-expression of BTG2 decreased cell migration and invasion in A549 and PC3 cancer cells. Furthermore, BTG2 expression was correlated with downregulation of focal adhesion kinase (FAK) Tyr576 and Tyr925 residues phosphorylation, while Tyr397 which is the autophosphorylation site was not influenced by BTG2 expression. c-Src phosphorylation which is the upstream of FAK was not influenced, whereas c-Src kinase activity was significantly decreased by BTG2 expression. BTG2 overexpression increased Src reduction state and inhibited reactive oxygen species (ROS) generation by being localized in mitochondria. Mitochondria-target BTG2 also inhibited cell migration via downregulation of Src-FAK signaling. In conclusion, our study reveals that BTG2 negatively regulated cancer cell migration by inhibiting Src activity through downregulation of ROS generation in mitochondria.

References

Mar 1, 1994·Molecular and Cellular Biology·M D SchallerJ T Parsons
Jun 18, 1993·Cell·J A Cooper, B Howell
Jun 7, 1996·Biochimica Et Biophysica Acta·M T Brown, J A Cooper
May 12, 2000·Nature Cell Biology·D J SiegD D Schlaepfer
Feb 2, 2002·Nature·Laura J van 't VeerStephen H Friend
Jul 13, 2004·Biochimica Et Biophysica Acta·David D SchlaepferDusko Ilic
Sep 30, 2004·International Journal of Cancer. Journal International Du Cancer·Sorina Grisaru-GranovskyRachel Bar-Shavit
Aug 3, 2005·Nature Reviews. Cancer·Gordon W McLeanMargaret C Frame
Jun 20, 2006·Molecular and Cellular Biology·Daniela PasseriFrancesco Grignani
Mar 14, 2008·The EMBO Journal·Fabienne MauxionBertrand Séraphin
Apr 9, 2008·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Tae Jun ParkIn Kyoung Lim
Jul 3, 2008·Cancer Research·Marcus SchmidtMathias Gehrmann
Oct 11, 2008·Free Radical Biology & Medicine·Ewa K KrasnowskaTiziana Parasassi
Mar 12, 2009·The Journal of Biological Chemistry·Masataka HoriuchiFuyuhiko Inagaki
May 4, 2010·Free Radical Biology & Medicine·Elisa GiannoniPaola Chiarugi
Dec 22, 2010·Biochemical and Biophysical Research Communications·Xu-Dong HuSaijun Fan

❮ Previous
Next ❯

Citations

Jul 17, 2013·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Qing SunGuangqiao Zeng
Jun 26, 2013·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·Dragana NikitovicGeorge Tzanakakis
Aug 2, 2013·Antioxidants & Redox Signaling·Elisa Giannoni, Paola Chiarugi
Nov 19, 2014·International Journal of Oncology·Bijing MaoGe Wang
May 2, 2014·European Journal of Pharmacology·Sina KardehAli Mohammad Alizadeh
Feb 18, 2014·Yonsei Medical Journal·Woon Ki PaikIn Kyoung Lim
Jul 18, 2017·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Jixi LiuJianzheng Jie
Dec 22, 2017·Signal Transduction and Targeted Therapy·Jingwen JiangCanhua Huang
Sep 30, 2014·The European Journal of Neuroscience·Beatriz G ArmendárizFerran Burgaya
Jun 20, 2018·Proceedings of the National Academy of Sciences of the United States of America·Jaewon J LeeMarcia C Haigis
Aug 1, 2018·Proceedings of the National Academy of Sciences of the United States of America·Hidekazu NaganoTomoaki Tanaka
Jan 10, 2019·Journal of Experimental & Clinical Cancer Research : CR·Yingjun XieYongsheng Yang

❮ Previous
Next ❯

Related Concepts

Related Feeds

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.

Adhesion Molecules in Health and Disease

Cell adhesion molecules are a subset of cell adhesion proteins located on the cell surface involved in binding with other cells or with the extracellular matrix in the process called cell adhesion. In essence, cell adhesion molecules help cells stick to each other and to their surroundings. Cell adhesion is a crucial component in maintaining tissue structure and function. Discover the latest research on adhesion molecule and their role in health and disease here.

Biophysics of Adhesion

Alterations in cell adhesion can disrupt important cellular processes and lead to a variety of diseases, including cancer and arthritis. It is also essential for infectious organisms, such as bacteria or viruses, to cause diseases. Understanding the biophysics of cell adhesion can help understand these diseases. Discover the latest research on the biophysics of adhesion here.