Aberrant hyperexpression of the RNA binding protein FMRP in tumors mediates immune evasion

摘要

INTRODUCTION: Cancer biology and therapy have been transformed by knowledge about immunoregulatory mechanisms that govern adaptive immunity. Although some forms of treatment resistance are related to the intentionally transitory operations of the adaptive immune system, others reflect more subtle requirements to modulate the immune system in different contexts. In this work, we identified an immunoregulatory mechanism involving the neuronal RNA binding protein fragile X mental retardation protein (FMRP), which broadly regulates protein translation and mRNA stability and is aberrantly up-regulated in multiple forms of cancer.RATIONALE: This study was motivated by reports that cancer cells naturally overexpressing FMRP, whose loss of expression in developing neurons causes cognitive defects, were invasive and metastatic. We investigated the expression of FMRP in human tumors, further assessed its tumor-promoting functions in mouse models of cancer, and evaluated its association with prognosis for human cancer patients.