PTEN and neoplasm: Given the fact that energy request tightly determines cell proliferation and survival of cancer cells, the elucidation of the mechanisms governing PTEN expression and function acquires important therapeutic implication for an extensive selection of human cancers and inheritable syndromes associated with abnormal signals regulated by PTEN. Notably, PTEN contributes to the regulation of reciprocal interplay between cancer cells and the TME, exerting in such a way a “tumor-suppressive/immune-protective effect”.