Nuclear p21-activated kinase 1 in breast cancer packs off tamoxifen sensitivity.
There is significant clinical interest in the factors that influence the development of tamoxifen resistance in estrogen receptor-alpha (ER-alpha)-positive breast cancers. Recent studies suggest that in ER-positive breast tumor cells, elevated protein levels, and in particular, nuclear localization of p21-activated kinase 1 (PAK1), is associated with the progressive limitation of tamoxifen sensitivity. These phenotypic effects of PAK1 in model systems are mechanistically linked with the ability of PAK1 to phosphorylate ER-alpha on serine 305 and subsequent secondary activation of serine 118. These findings prompt further investigation of how nuclear signaling by PAK1 may affect estrogen's action and whether tamoxifen resistance might be prevented or reversed by PAK1 inhibition.
Rayala
Suresh K
SK
Department of Molecular and Cellular Oncology, The University of Texas M.D. Anderson Cancer Center, Texas 77030, USA.
Molli
Poonam R
PR
Kumar
Rakesh
R
D000818:Animals; D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000201:enzymology*; D006801:Humans; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013629:Tamoxifen / Q000494:pharmacology*; D054462:p21-Activated Kinases
D018931:Antineoplastic Agents, Hormonal; D013629:Tamoxifen; C515903:PAK1 protein, human; D017346:Protein Serine-Threonine Kinases; D054462:p21-Activated Kinases