Carboxyl-terminal modulator protein positively regulates Akt phosphorylation and acts as an oncogenic driver in breast cancer

Yu Peng Liu, Wen Chi Liao, Luo Ping Ger, Jiun Chin Chen, Tai I. Hsu, Yu Cheng Lee, Hong Tai Chang, Yu Chia Chen, Yi Hua Jan, Kuen Haur Lee, Yu Hao Zeng, Michael Hsiao, Pei Jung Lu

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14 Citations (Scopus)

Abstract

Akt activation has been implicated broadly in tumorigenesis, but the basis for its dysregulation in cancer cells is incompletely understood. In this study, we sought to clarify a regulatory role for the Akt-binding carboxy-terminal modulator protein (CTMP), which has been controversial. In evaluating CTMP expression in paired normaltumor specimens of 198 patients with breast cancer, we found that CTMP was upregulated in breast tumors, where it was associated with poor patient survival. Notably, CTMP expression also correlated positively with Akt phosphorylation in breast cancer clinical specimens and cell lines. Furthermore, ectopic expression of CTMP promoted cell proliferation and enhanced the tumorigenic properties of estrogen-dependent breast cancer cells. This effect was correlated with increased sensitivity to insulin-induced Akt phosphorylation, which is mediated primarily by the phosphoinositide 3-kinase-Akt pathway. In contrast, short hairpin RNA-mediated silencing of endogenous CTMP decreased the proliferation of estrogen-dependent or estrogen-independent breast cancer cells. Mechanistic investigations defined the N-terminal domain of CTMP at amino acids 1 to 64 as responsible for Akt binding. Taken together, our results firmly corroborate the concept that CTMP promotes Akt phosphorylation and functions as an oncogenic molecule in breast cancer.

Original languageEnglish
Pages (from-to)6194-6205
Number of pages12
JournalCancer Research
Volume73
Issue number20
DOIs
Publication statusPublished - Oct 15 2013

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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    Liu, Y. P., Liao, W. C., Ger, L. P., Chen, J. C., Hsu, T. I., Lee, Y. C., Chang, H. T., Chen, Y. C., Jan, Y. H., Lee, K. H., Zeng, Y. H., Hsiao, M., & Lu, P. J. (2013). Carboxyl-terminal modulator protein positively regulates Akt phosphorylation and acts as an oncogenic driver in breast cancer. Cancer Research, 73(20), 6194-6205. https://doi.org/10.1158/0008-5472.CAN-13-0518