UNASSIGNED: Intratumoral heterogeneity helps drive the selection for diverse therapy-resistant cell populations. In this study, we demonstrate the coexistence of two therapy-resistant populations with distinct properties that are reproducibly enriched under conditions that characterize tumor pathophysiology. Breast cancer cells that survived chemotherapy or hypoxia were enriched for cells expressing the major hyaluronic acid receptor @entity1759 . However, only @entity1759 (hi) cells that survived chemotherapy exhibited cancer stem cell (CSC) phenotypes based on growth potential and gene expression signatures that represent oncogenic signaling and metastatic prowess. Strikingly, we identified @entity6474 as a key growth promoter of @entity1759 (hi) cells that survived chemotherapy but also as a growth inhibitor of cells that survived hypoxia. Expression of the TGFb receptor @entity7382 and its effector molecule @entity1594 was required for enrichment of @entity1759 (hi) cells exposed to the chemotherapeutic drug @entity1259 , which suggests a feed-forward loop to enrich for and enhance the function of surviving CSCs. Our results reveal context-dependent effects of @entity6474 signaling in the same tumor at the same time. The emergence of distinct resistant tumor cell populations as a consequence of prior therapeutic intervention or microenvironmental cues has significant implications for the responsiveness of recurring tumors to therapy. Cancer Res; 75(21); 1-12.   2015 AACR.

Breast Cancer Cells Respond Differentially to Modulation of XXXX Signaling after Exposure to Chemotherapy or Hypoxia.

@entity7382 :: ('7046', 'Gene') :: ['TGFbR1'] @entity1259 :: ('MESH:D015251', 'Chemical') :: ['epirubicin'] @entity1759 :: ('960', 'Gene') :: ['CD44'] @entity1594 :: ('4089', 'Gene') :: ['SMAD4'] @entity6474 :: ('7042', 'Gene') :: ['TGFb2']
@entity6474 :: (7042,Gene) :: ['TGFb2']
