P21 activated kinase-1 mediates transforming growth factor β1-induced prostate cancer cell epithelial to mesenchymal transition

Biochimica Et Biophysica Acta
Ahmad Al-AzayzihPayaningal R Somanath

Abstract

Transforming growth factor beta (TGFβ) is believed to play a dual role in prostate cancer. Molecular mechanism by which TGFβ1 suppresses early prostate tumor growth and induces epithelial-to-mesenchymal transition (EMT) in advanced stages is not known. We determined if P21-activated kinase1 (Pak1), which mediates cytoskeletal remodeling is necessary for the TGFβ1 induced prostate cancer EMT. Effects of TGFβ1 on control prostate cancer PC3 and DU145 cells and those with IPA 3 and siRNA mediated Pak1 inhibition were tested for prostate tumor xenograft in vivo and EMT in vitro. TGFβ1 inhibited PC3 tumor xenograft growth via activation of P38-MAPK and caspase-3, 9. Long-term stimulation with TGFβ1 induced PC3 and DU145 cell scattering and increased expression of EMT markers such as Snail and N-cadherin through tumor necrosis factor receptor-associated factor-6 (TRAF6)-mediated activation of Rac1/Pak1 pathway. Selective inhibition of Pak1 using IPA 3 or knockdown using siRNA both significantly inhibited TGFβ1-induced prostate cancer cell EMT and expression of mesenchymal markers. Our study demonstrated that TGFβ1 induces apoptosis and EMT in prostate cancer cells via activation of P38-MAPK and Rac1/Pak1 respectively. Our results rev...Continue Reading

References

Apr 1, 1986·Journal of Surgical Oncology·D M EuhusF E Johnson
Mar 30, 2001·The Journal of Biological Chemistry·F YangZ Sun
Jun 18, 2003·Cell·Yigong Shi, Joan Massagué
Oct 24, 2003·The Journal of Biological Chemistry·Nicolas SchrantzGary M Bokoch
Jul 5, 2005·Cellular Signalling·Liron Even-FaitelsonShoshana Ravid
Aug 18, 2005·Journal of Cell Science·Aristidis Moustakas, Carl-Henrik Heldin
Nov 18, 2006·Cell·Gaorav P Gupta, Joan Massagué
Jul 11, 2007·International Journal of Cancer. Journal International Du Cancer·Gerald C O'SullivanOrla P Barry
Apr 22, 2008·Cellular Signalling·Tasneem AhmedClaire M Wells
Dec 3, 2008·International Journal of Cancer. Journal International Du Cancer·Kiwon S YooJohn J Krolewski
Sep 3, 2009·Molecular Cancer Therapeutics·Julien Viaud, Jeffrey R Peterson
Dec 1, 2009·Cell·Jean Paul ThieryM Angela Nieto
May 29, 2010·Expert Opinion on Therapeutic Targets·Julia V KichinaEugene S Kandel
Jun 22, 2011·Nature Reviews. Urology·Jones T Nauseef, Michael D Henry
Jun 28, 2011·Cell and Tissue Research·Yabing MuMaréne Landström
Oct 19, 2012·Cell Adhesion & Migration·Bethany N Smith, Valerie A Odero-Marah
Apr 12, 2013·Cancer Research·Luis E Arias-RomeroJonathan Chernoff
Jan 9, 2014·CA: a Cancer Journal for Clinicians·Rebecca SiegelAhmedin Jemal
Feb 25, 2014·Biochimica Et Biophysica Acta·Aristidis Moustakas, Paraskevi Heldin
Mar 25, 2014·Small GTPases·Chetan K Rane, Audrey Minden
Apr 25, 2014·Annals of Oncology : Official Journal of the European Society for Medical Oncology·M MalvezziE Negri
Jun 4, 2014·Mediators of Inflammation·Joanna Magdalena Zarzynska
Jul 6, 2014·The Journal of Pharmacology and Experimental Therapeutics·Ahmed AlhusbanPayaningal R Somanath

❮ Previous
Next ❯

Citations

Dec 22, 2015·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Zhihong WangLiang He
Apr 27, 2016·Cellular and Molecular Life Sciences : CMLS·Fei GaoPayaningal R Somanath
May 28, 2016·BMC Cancer·Muraleedharan ParvathyMadhavan Radhakrishna Pillai
Apr 9, 2017·Developmental Dynamics : an Official Publication of the American Association of Anatomists·Hendrik UngefrorenHendrik Lehnert
Mar 30, 2018·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Xing-Hua XiaoLi-Xia Xiong
Mar 6, 2018·Journal of Cellular and Molecular Medicine·Cinzia AntognelliVincenzo N Talesa
Dec 2, 2017·Journal of Cellular and Molecular Medicine·Lei ChenZhi-Jun Sun
Jul 23, 2016·Experimental Biology and Medicine·Karen M DoerschWarren E Zimmer
Jun 2, 2018·Journal of Cellular Physiology·Harika SabbineniPayaningal R Somanath
Oct 27, 2017·Acta Biochimica Et Biophysica Sinica·Jianguo Song, Weiwei Shi
Sep 14, 2019·Pharmacology Research & Perspectives·Wided Najahi-MissaouiBrian S Cummings
Oct 24, 2018·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Jan Moritz PonertMartin Schlesinger
Apr 3, 2020·Biochemical Pharmacology·Arti VermaPayaningal R Somanath
Jun 14, 2021·Biochemical and Biophysical Research Communications·Misa Nozaki, Makoto Nishizuka

❮ Previous
Next ❯

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.

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis

Apoptosis in Cancer

Apoptosis is an important mechanism in cancer. By evading apoptosis, tumors can continue to grow without regulation and metastasize systemically. Many therapies are evaluating the use of pro-apoptotic activation to eliminate cancer growth. Here is the latest research on apoptosis in cancer.

Apoptotic Caspases

Apoptotic caspases belong to the protease enzyme family and are known to play an essential role in inflammation and programmed cell death. Here is the latest research.

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.