Riecken, LB;
Zoch, A;
Wiehl, U;
Reichert, S;
Scholl, I;
Cui, Y;
Ziemer, M;
... Morrison, H; + view all
(2016)
CPI-17 drives oncogenic Ras signaling in human melanomas via Ezrin-Radixin-Moesin family proteins.
Oncotarget
, 7
(48)
pp. 78242-78254.
10.18632/oncotarget.12919.
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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.
| Type: | Article |
|---|---|
| Title: | CPI-17 drives oncogenic Ras signaling in human melanomas via Ezrin-Radixin-Moesin family proteins |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.18632/oncotarget.12919 |
| Publisher version: | http://dx.doi.org/10.18632/oncotarget.12919 |
| Language: | English |
| Additional information: | This work is licensed under a Creative Commons Attribution 3.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. |
| Keywords: | Science & Technology, Life Sciences & Biomedicine, Oncology, Cell Biology, Cpi-17, Erm, Ras, Cancer, Melanoma, Suppressor Gene-Product, Erm Proteins, Inhibitory Protein, Cell Cortex, Merlin, Growth, Phosphorylation, Phosphatase, Activation, Expression |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences |
| URI: | https://discovery.ucl.ac.uk/id/eprint/1537383 |
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