CCL2, survivin and autophagy: new links with implications in human cancer

Recent data strongly support the idea that the orchestrated interaction between cancer and other cells in the tumor microenvironment is a vital component in the neoplastic process. Thus, tumor cells take advantage of the signaling molecules of the immune system to proliferate, survive, and invade other tissues. CCL2 (Chemokine (C-C motif) ligand 2, Monocyte chemoattractant protein-1 (MCP-1) has been demonstrated to play a significant role in prostate cancer neoplasia and invasion, and is highly expressed in the tumor microenvironment. We recently reported that CCL2 elicits a strong survival advantage in prostate cancer PC3 cells through PI3K/Akt-dependent regulation of autophagy via the mammalian target of rapamycin (mTOR) pathway and importantly, survivin upregulation is essential in this survival mechanism. Autophagy protects cells from nutrient depletion stress, but, paradoxically, excessive autophagy will result in cell death. How these life or death decisions are regulated remains unclear. Here we discuss the function of survivin in the control of autophagy and the interaction between CCL2, survivin and autophagy in the complex program of tumor progression.