CPI-17 drives oncogenic Ras signaling in human melanomas via Ezrin-Radixin-Moesin family proteins.
Oncotarget
; 7(48): 78242-78254, 2016 Nov 29.
Article
in En
| MEDLINE
| ID: mdl-27793041
ABSTRACT
Hyperactive Ras signaling has strong oncogenic effects causing several different forms of cancer. Hyperactivity is frequently induced by mutations within Ras itself, which account for up to 30% of all human cancers. In addition, hyperactive Ras signaling can also be triggered independent of Ras by either mutation or by misexpression of various upstream regulators and immediate downstream effectors. We have previously reported that C-kinase potentiated protein phosphatase-1 inhibitor of 17 kDa (CPI-17) can drive Ras activity and promote tumorigenic transformation by inhibition of the tumor suppressor Merlin. We now describe an additional element of this oncogenic mechanism in the form of the ezrin-radixin-moesin (ERM) protein family, which exhibits opposing roles in Ras activity control. Thus, CPI-17 drives Ras activity and tumorigenesis in a two-fold way; inactivation of the tumor suppressor merlin and activation of the growth promoting ERM family. The in vivo significance of this oncogenic switch is highlighted by demonstrating CPI-17's involvement in human melanoma pathogenesis.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Skin Neoplasms
/
Phosphoprotein Phosphatases
/
Ras Proteins
/
Cytoskeletal Proteins
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Melanoma
/
Membrane Proteins
/
Microfilament Proteins
Limits:
Animals
/
Humans
Language:
En
Journal:
Oncotarget
Year:
2016
Document type:
Article
Affiliation country:
Alemania