Reciprocal regulation of signaling and endocytosis: Implications for the evolving cancer cell

Abstract

Cell surface receptor uptake via clathrin-mediated endocytosis (CME) and subsequent intracellular sorting for degradation or recycling regulates the strength and specificity of downstream signaling. Signaling, in turn, modulates early endocytic trafficking. This reciprocal regulation of signaling and endocytosis provides opportunities for the establishment of feedback loops to enhance or suppress surface-derived signals. Recent studies suggest that dynamin-1, a presumed neuron-specific isoform of the large, membrane fission GTPase, can be activated in nonneuronal cells downstream of cancer-relevant signaling pathways and thereby function as a nexus between signaling and early endocytic trafficking. I speculate that sustained up-regulation and/or acute activation of dynamin-1 in cancer cells contributes to a program of "adaptive" CME that alters signaling to enhance cancer cell survival, migration, and proliferation.