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2015 ; 75
(10
): 1992-2004
Nephropedia Template TP
gab.com Text
Twit Text FOAVip
Twit Text #
English Wikipedia
The endogenous cell-fate factor dachshund restrains prostate epithelial cell
migration via repression of cytokine secretion via a cxcl signaling module
#MMPMID25769723
Chen K
; Wu K
; Jiao X
; Wang L
; Ju X
; Wang M
; Di Sante G
; Xu S
; Wang Q
; Li K
; Sun X
; Xu C
; Li Z
; Casimiro MC
; Ertel A
; Addya S
; McCue PA
; Lisanti MP
; Wang C
; Davis RJ
; Mardon G
; Pestell RG
Cancer Res
2015[May]; 75
(10
): 1992-2004
PMID25769723
show ga
Prostate cancer is the second leading form of cancer-related death in men. In a
subset of prostate cancer patients, increased chemokine signaling IL8 and IL6
correlates with castrate-resistant prostate cancer (CRPC). IL8 and IL6 are
produced by prostate epithelial cells and promote prostate cancer cell invasion;
however, the mechanisms restraining prostate epithelial cell cytokine secretion
are poorly understood. Herein, the cell-fate determinant factor DACH1 inhibited
CRPC tumor growth in mice. Using Dach1(fl/fl)/Probasin-Cre bitransgenic mice, we
show IL8 and IL6 secretion was altered by approximately 1,000-fold by endogenous
Dach1. Endogenous Dach1 is shown to serve as a key endogenous restraint to
prostate epithelial cell growth and restrains migration via CXCL signaling. DACH1
inhibited expression, transcription, and secretion of the CXCL genes (IL8 and
IL6) by binding to their promoter regulatory regions in chromatin. DACH1 is thus
a newly defined determinant of benign and malignant prostate epithelium cellular
growth, migration, and cytokine abundance in vivo.