Biological role of phosphatase PTEN in cancer and tissue injury healing

PTEN (phosphatas and tensin homolog deleted on chromosome ten) also referred to as MMAC (mutated in multiple advanced cancers) was discovered as a tumor suppressor gene and later found to be a phospholipid phosphatas. PTEN negatively regulates Akt activation by preventing its phosphorylation. PTEN there fore inhibits the PI 3-kinas/Akt signaling pathway which is important for cell growth and survival. Overexpression or enhanced activation of PTEN can potentially impair injury healing by at least 4 mechanisms. PTEN can: 1) inhibit entry into the cell cycle by inhibiting G1 to S phase progression and arrest cell proliferation required for tissue reconstruction during injury h aling; 2) incr as apoptosis by blocking Akt activation leading to increased Bad and Caspase- 9 activities; 3) inhibit hypoxia-induced angiogenesis required for injury healing by blocking Akt-mediated VEGF gene transcription; 4) inhibit Akt-mediated cell migration, i.e. re-epithelialization, which is also required for injury healing. The same mechanisms can also suppress cancer growth and metastases. Therefore, elucidating the role of the PTEN/PI 3-kinase/Akt pathway will likely advance our knowledge of the mechanisms controlling the processes of injury healing and cancer growth.