Src kinases catalytic activity regulates proliferation, migration and invasiveness of MDA-MB-231 breast cancer cells

Cellular Signalling
María Pilar Sánchez-BailónJorge Martín-Pérez

Abstract

SFKs are frequently deregulated in cancer where they control cellular proliferation, migration, survival and metastasis. Here we study the role of SFKs catalytic activity in triple-negative/basal-like and metastatic human breast cancer MDA-MB-231 cells employing three well-established inhibitors: Dasatinib, PP2 and SU6656. These compounds inhibited migration and invasion. Concomitantly, they reduced Fak, paxillin, p130CAS, caveolin-1 phosphorylation and altered cytoskeletal structures. They also inhibited cell proliferation, but in different manners. Dasatinib and PP2 increased p27(Kip1) expression and reduced c-Myc levels, restraining G1–S transition. In contrast, SU6656 did not modify p27(Kip1) expression, slightly altered c-Myc levels and generated polyploid multinucleated cells, indicating inhibition of cytokinesis. These later effects were also observed in SYF fibroblasts, suggesting a SFKs-independent action. ZM447439, an Aurora B kinase inhibitor, produced similar cell cycle and morphological alterations in MDA-MB-231 cells, indicating that SU6656 blocked Aurora B kinase. This was confirmed by inhibition of histone H3 phosphorylation, the canonical Aurora B kinase substrate. Furthermore, hierarchical clustering analysis ...Continue Reading

References

Jan 1, 1997·Annual Review of Cell and Developmental Biology·S M Thomas, J S Brugge
May 6, 1999·The EMBO Journal·R A KlinghofferP Soriano
Jul 14, 2001·Molecular Biology of the Cell·J A Fresno VaraJ Martín-Pérez
Apr 30, 2003·The Journal of Cell Biology·Claire DitchfieldStephen S Taylor
May 4, 2005·Trends in Cell Biology·Régis GietClaude Prigent
Oct 4, 2005·Proceedings of the National Academy of Sciences of the United States of America·Aravind SubramanianJill P Mesirov
Oct 6, 2005·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Faye M JohnsonNicholas J Donato
Jan 24, 2006·Anti-cancer Drugs·Ting ChenChristopher C Taylor
Mar 17, 2006·Breast Cancer Research and Treatment·Marijke WasielewskiMieke Schutte
May 27, 2006·The Journal of Biological Chemistry·Lorena GonzálezJorge Martín-Pérez
Aug 18, 2006·Nature Reviews. Cancer·Andrea H BildJoseph R Nevins
Sep 14, 2007·The Biochemical Journal·Jenny BainPhilip Cohen
Feb 4, 2009·Cancer Metastasis Reviews·Nicholas Keen, Stephen Taylor
Apr 29, 2009·Cancer Letters·Jyoti NautiyalAdhip P N Majumdar
Jul 4, 2009·Cancer Cell·Xiang H-F ZhangJoan Massagué
Feb 5, 2010·Cancer Cell·Swarna MehrotraDario C Altieri
Feb 24, 2010·Molecular Cancer·Christopher P GullyMong-Hong Lee
Jul 17, 2010·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Erica L Mayer, Ian E Krop

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Citations

Dec 10, 2013·The Journal of Clinical Investigation·Lara H El TounyJeffrey E Green
Jun 13, 2013·Biochimica Et Biophysica Acta·Caroline E Nunes-XavierRafael Pulido
Jan 1, 2014·Journal of Clinical Medicine·Philippe Beuzeboc, Suzy Scholl
Feb 3, 2016·The Journal of Cell Biology·Edward R HortonMartin J Humphries
Apr 1, 2015·International Journal of Oncology·Vincent BlanckaertBenoît Chénais
Aug 1, 2014·Journal of Cellular Biochemistry·Bernardo Nuche-BerenguerR T Jensen
May 3, 2014·International Journal of Cancer. Journal International Du Cancer·Lei ZhongSheng-Yong Yang
Jan 21, 2014·Biochimica Et Biophysica Acta·Juan Carlos Gallardo-PérezSara Rodríguez-Enríquez
Apr 16, 2015·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Jian Ying HeZhi Li Liu
Nov 28, 2013·The International Journal of Biochemistry & Cell Biology·Iwona CichaMargarete Goppelt-Struebe
Jun 18, 2016·Clinical and Experimental Pharmacology & Physiology·Yinliang QiShuyu Gui
Jun 28, 2017·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Shimaa M HassounMamdouh M El-Shishtawy
Nov 29, 2017·PloS One·Víctor Mayoral-VaroJorge Martín-Pérez
May 20, 2015·Oncotarget·María Pilar Sánchez-BailónJorge Martín-Pérez
Apr 11, 2017·International Journal of Oncology·Mengnan ZhangXueqing Chen
Oct 27, 2018·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Charles HellecFabrice Allain
Dec 11, 2019·Cell Death & Disease·Marie-Ange Djeungoue-PetgaEtienne Hebert-Chatelain
May 8, 2016·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Rabia A GilaniMatthew B Soellner
Oct 15, 2020·International Journal of Molecular Sciences·Sonia AlcaláBruno Sainz
Apr 12, 2021·Seminars in Cancer Biology·Jing ZhangXinzhe Liu
Jun 15, 2021·Frontiers in Pharmacology·Meng LiYang Zhang

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