The multiple layers of non-genetic regulation of PTEN tumour suppressor activity.
Mutations and deletions of the tumour suppressor phosphatase and tensin homologue deleted on chromosome 10 (PTEN) are frequently involved in the development of cancer. However, PTEN is also tightly controlled by various non-genomic mechanisms. This review focuses on those mechanisms, namely on the epigenetic silencing of PTEN, post-transcriptional regulation by non-coding RNAs and post-translational modification. We summarise their involvement in cancer in general, and place some emphasis on leukaemia, where PTEN genetic lesions are relatively uncommon and, strikingly, high levels of PTEN expression frequently associate with PTEN functional inactivation. Overall, it is apparent that rather than looking strictly for PTEN genetic lesions and PTEN expression status, the key to evaluating the real impact of PTEN as a 'quasi-insufficient' tumour suppressor must rely on the complete understanding of PTEN's 'functional dose', incorporating the multiple layers of PTEN regulation in the cell that are ultimately compromised in a given cancer.
Instituto de Medicina Molecular, Faculdade de Medicina da Universidade de Lisboa, 1649-028 Lisbon, Portugal.
Nádia C
NC
Correia
Instituto de Medicina Molecular, Faculdade de Medicina da Universidade de Lisboa, 1649-028 Lisbon, Portugal.
Ana
A
Gírio
Instituto de Medicina Molecular, Faculdade de Medicina da Universidade de Lisboa, 1649-028 Lisbon, Portugal.
Inês
I
Antunes
Instituto de Medicina Molecular, Faculdade de Medicina da Universidade de Lisboa, 1649-028 Lisbon, Portugal.
Leila R
LR
Martins
Instituto de Medicina Molecular, Faculdade de Medicina da Universidade de Lisboa, 1649-028 Lisbon, Portugal. Electronic address: joao_barata@fm.ul.pt.
João T
JT
Barata
D000818:Animals; D045744:Cell Line, Tumor; D057890:Epigenomics; D016147:Genes, Tumor Suppressor; D006801:Humans; D009369:Neoplasms / Q000201:enzymology*; D051059:PTEN Phosphohydrolase / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction
D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human
Cancer; Epigenetic, transcriptional, post-transcriptional and post-translational regulation; Leukaemia; Non-genetic inactivation; PI3K–Akt/PKB pathway; PTEN; Tumour suppressor