A2 Vertaisarvioitu katsausartikkeli tieteellisessä lehdessä
Cancerous Inhibitor of Protein Phosphatase 2A, an Emerging Human Oncoprotein and a Potential Cancer Therapy Target
Tekijät: Khanna A, Pimanda JE, Westermarck J
Kustantaja: AMER ASSOC CANCER RESEARCH
Kustannuspaikka: PHILADELPHIA; 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
Julkaisuvuosi: 2013
Journal: Cancer Research
Tietokannassa oleva lehden nimi: Cancer research
Lehden akronyymi: Cancer Res.
Numero sarjassa: 23
Vuosikerta: 73
Numero: 23
Aloitussivu: 6548
Lopetussivu: 6553
Sivujen määrä: 6
ISSN: 0008-5472
DOI: https://doi.org/10.1158/0008-5472.CAN-13-1994
Tiivistelmä
Protein phosphatase 2A (PP2A) complexes function as tumor suppressors by inhibiting the activity of several critical oncogenic signaling pathways. Consequently, inhibition of the PP2A phosphatase activity is one of many prerequisites for the transformation of normal human cells into cancerous cells. However, mechanisms for PP2A inactivation in human cancers are poorly understood. The aberrant expression of cancerous inhibitor of protein phosphatase 2A (CIP2A), a recently identified endogenous PP2A inhibitor in malignant cells, is one such mechanism. Various independent studies have validated CIP2A's role in promoting tumor growth and resistance to apoptosis and senescence-inducing therapies. Notably, high CIP2A expression predicts poor patient prognosis in several human cancer types. Among the oncogenic proteins dephosphorylated by PP2A, the MYC oncoprotein, which is phosphorylated at serine 62, has surfaced as a marker for the oncogenic activity of CIP2A. The positive-feedback loop between CIP2A and MYC augments the activity of MYC in cancer cells. In addition, CIP2A promotes the phosphorylation and activity of additional oncoproteins, including E2F1 and AKT. However, CIP2A is not essential for normal mouse growth and development. These findings indicate that CIP2A is a novel anticancer target based on PP2A reactivation and inhibition of the oncogenic activity of its downstream effectors. The potential approaches and feasibility of targeting CIP2A are discussed here. (C) 2013 AACR.
Protein phosphatase 2A (PP2A) complexes function as tumor suppressors by inhibiting the activity of several critical oncogenic signaling pathways. Consequently, inhibition of the PP2A phosphatase activity is one of many prerequisites for the transformation of normal human cells into cancerous cells. However, mechanisms for PP2A inactivation in human cancers are poorly understood. The aberrant expression of cancerous inhibitor of protein phosphatase 2A (CIP2A), a recently identified endogenous PP2A inhibitor in malignant cells, is one such mechanism. Various independent studies have validated CIP2A's role in promoting tumor growth and resistance to apoptosis and senescence-inducing therapies. Notably, high CIP2A expression predicts poor patient prognosis in several human cancer types. Among the oncogenic proteins dephosphorylated by PP2A, the MYC oncoprotein, which is phosphorylated at serine 62, has surfaced as a marker for the oncogenic activity of CIP2A. The positive-feedback loop between CIP2A and MYC augments the activity of MYC in cancer cells. In addition, CIP2A promotes the phosphorylation and activity of additional oncoproteins, including E2F1 and AKT. However, CIP2A is not essential for normal mouse growth and development. These findings indicate that CIP2A is a novel anticancer target based on PP2A reactivation and inhibition of the oncogenic activity of its downstream effectors. The potential approaches and feasibility of targeting CIP2A are discussed here. (C) 2013 AACR.
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