Parvin-beta inhibits breast cancer tumorigenicity and promotes CDK9-mediated peroxisome proliferator-activated receptor gamma 1 phosphorylation.
Parvin-beta is a focal adhesion protein downregulated in human breast cancer cells. Loss of Parvin-beta contributes to increased integrin-linked kinase activity, cell-matrix adhesion, and invasion through the extracellular matrix in vitro. The effect of ectopic Parvin-beta expression on the transcriptional profile of MDA-MB-231 breast cancer cells, which normally do not express Parvin-beta, was evaluated. Particular emphasis was placed upon propagating MDA-MB-231 breast cancer cells in three-dimensional culture matrices. Interestingly, Parvin-beta reexpression in MDA-MB-231 cells increased the mRNA expression, serine 82 phosphorylation (mediated by CDK9), and activity of the nuclear hormone receptor peroxisome proliferator-activated receptor gamma (PPARgamma), and there was a concomitant increase in lipogenic gene expression as a downstream effector of PPARgamma. Importantly, Parvin-beta suppressed breast cancer growth in vivo, with associated decreased proliferation. These data suggest that Parvin-beta might influence breast cancer progression.
Johnstone
Cameron N
CN
Department of Medicine, Abramson Cancer Center, University of Pennsylvania, 600 Clinical Research Building, 415 Curie Blvd., Philadelphia, PA 19104, USA.
Mongroo
Perry S
PS
Rich
A Sophie
AS
Schupp
Michael
M
Bowser
Mark J
MJ
Delemos
Andrew S
AS
Tobias
John W
JW
Liu
Yingqiu
Y
Hannigan
Gregory E
GE
Rustgi
Anil K
AK
D000185:Actinin / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D042863:Cyclin-Dependent Kinase 9 / Q000235:genetics / Q000378:metabolism*; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D050356:Lipid Metabolism; D051379:Mice; D009368:Neoplasm Transplantation; D047495:PPAR gamma / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D010768:Phosphoserine / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D014158:Transcription, Genetic / Q000235:genetics
C486591:PARVB protein, human; D047495:PPAR gamma; D012333:RNA, Messenger; D000185:Actinin; D010768:Phosphoserine; D042863:Cyclin-Dependent Kinase 9