@entity9486 and XXXX Regulate Emergence of Aggressive Cancer Stem-like Features via miR-885-5p Control.

@entity9486 @entity1 @entity4729 @entity5439 @entity2440 @entity5 @entity2 @entity2856 @entity320
UNASSIGNED: @entity5 stem-like cells (CSC) have been proposed to promote @entity5 progression by initiating @entity5 growth at distant sites, suggesting that stem-like cell features can support metastatic efficiency. Here, we demonstrate that oncogenic DNp73, a @entity5 -suppressor @entity9486 , confers @entity5 cells with enhanced stem-like properties. DNp73 overexpression in noninvasive @entity320 and @entity2 cells increased anchorage-independent growth and elevated the expression of the pluripotency factors @entity5439 , @entity2440 , and @entity4729 . Conversely, DNp73 depletion in metastatic cells downregulated stemness genes, attenuated sphere formation and reduced the @entity5 -initiating capability of spheroids in @entity5 xenograft models. Mechanistic investigations indicated that DNp73 acted by attenuating expression of miR-885-5p, a direct regulator of the @entity2856 ( @entity2856 ) responsible for stemness marker expression. Modulating this pathway was sufficient to enhance chemosensitivity, overcoming DNp73-mediated drug resistance. Clinically, we established a correlation between low @entity9486 function and high @entity2856 / @entity5439 / @entity2440 / @entity4729 levels in @entity320 specimens that associated with reduced @entity1 survival. Our work shows how DNp73 promotes @entity5 stem-like features and provides a mechanistic rationale to target the DNp73- @entity2856 cascade as a therapeutic strategy to eradicate CSC. @entity5 Res; 76(2); 197-205.   2015 AACR.
