RARγ Controls the Behavior of Normal and Cancer Stem Cells

Retinoic acid receptor (RAR) g expression is restricted during adult haematopoiesis to haematopoietic stem cells and their immediate offspring and required for their maintenance. From zebrafish studies, RARg is selectively expressed by stem cells and agonism in the absence of exogenous all-trans retinoic acid blocked stem cell development. Recent findings for the expression of RARg have revealed an oncogenic role in acute myeloid leukaemia and cholangiocarcinoma, and colorectal, head and neck, hepatocellular, ovarian, pancreatic, prostate, and renal cancer. Overexpression and agonism of RARg enhanced cell proliferation for head and neck, hepatocellular, and prostate cancer. RARg antagonism, pan-RAR antagonism, and RARg downregulation led to cell growth which was often followed by cell death for acute myeloid leukaemia, astrocytoma and cholangiocarcinoma, and hepatocellular, primitive neuroectodermal, ovarian, and prostate cancer. Histological studies have associated high level RARg expression with high grade disease, metastasis, and a poor prognosis, for cholangiocarcinoma and ovarian, pancreatic, and prostate cancer. RARg is expressed by cancer stem cells and a targetable drive of cancer cell growth and survival.