miR-138-Mediated Regulation of XXXX Expression Modulates Sensitivity to Chemotherapeutics.

@entity1 @entity263 @entity5 @entity43166 @entity2 @entity342 @entity1205
UNASSIGNED: @entity263 is the second leading cause of @entity5 in @entity1 , second only to @entity2 , mainly due to disease reoccurrence as a result to lack of response to @entity342 deprivation therapies (ADT) after castration. @entity1 with metastatic castration-resistant @entity263 (mCRPC) have very limited treatment options, with @entity1205 as the first-line standard of care, for which resistance to this chemotherapeutic ultimately develops. Therefore, finding ways to sensitize @entity5 to chemotherapies and to limit chemoresistance provides a viable strategy to extend the survival of mCRPC @entity1 . This study investigated the role of @entity43166 ( @entity43166 /K2), a member of the Kindlin family of FERM domain proteins and key regulators of the adhesive functions mediated by integrin, in the sensitization of mCRPC to chemotherapeutics. Loss of K2, which is overexpressed in @entity263 cells derived from mCRPC @entity5 , compared with those cells derived from @entity342 -dependent @entity5 , significantly enhanced apoptosis and cell death of @entity1205 -treated PC3 cells. Furthermore, it was determined that K2-mediated sensitization to @entity1205 treatment is the result of inhibition of b1-integrin signaling. Finally, miR-138 specifically targeted K2 and inhibited its expression, thereby regulating a miR-138/K2/b1-integrin signaling axis in mCRPC that is critical for the modulation of sensitivity to chemotherapeutics. Thus, these data identify a novel signaling axis where K2 in combination with chemotherapeutics provides a new target for the treatment of mCRPC. IMPLICATIONS: Targeted inhibition of @entity43166 in combination with chemotherapy represents an effective treatment option for mCRPC. Mol Cancer Res; 14(2); 1-11.   2015 AACR.
