Phosphatase and tensin homolog deleted on chromosome 10 (PTEN) and PH domain and leucine-rich repeat phosphatase cross-talk (PHLPP) in cancer cells and in transforming growth factor ß-activated stem cells.
J Biol Chem
; 289(17): 11601-11616, 2014 Apr 25.
Article
em En
| MEDLINE
| ID: mdl-24599953
ABSTRACT
Akt kinase controls cell survival, proliferation, and invasive growth and is a critical factor for cancer development. Here we describe a cross-talk between phosphatases that may preserve levels of activated/phosphorylated Akt and confer aggressive growth of cancer cells. In prostatic cancer cells, but not in non-transformed cells or in prostate stem cells, we found that the phosphatase and tensin homolog deleted on chromosome 10 (PTEN) overexpression down-regulated PH domain and leucine-rich repeat phosphatase (PHLPP) and that PHLPP overexpression down-regulated PTEN. We also show that silencing PTEN by siRNA increased the levels of PHLPPs. This cross-talk facilitated invasive migration and was mediated by epigenetic alterations, including activation of miR-190, miR-214, polycomb group of proteins, as well as DNA methylation. A role for the purinergic receptor P2X4, previously associated with wound healing, was indicated. We also show that TGF-ß1 induced cross-talk concomitant with epithelial-mesenchymal transition in stem cells. The cross-talk emerged as an integrated part of epithelial-mesenchymal transition. We conclude that cross-talk between PTEN and PHLPPs is silenced in normal prostate cells but activated in TGF-ß1 transformed prostate stem and cancer cells and facilitates invasive growth.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias da Próstata
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Células-Tronco
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Proteínas Nucleares
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Fator de Crescimento Transformador beta
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Fosfoproteínas Fosfatases
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PTEN Fosfo-Hidrolase
Limite:
Animals
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Humans
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Male
Idioma:
En
Ano de publicação:
2014
Tipo de documento:
Article