Carboxyl-terminal modulator protein facilitates tumor metastasis in triple-negative breast cancer

Cheng Han Lin, Wen Der Lin, Yun Chin Huang, Yu Chia Chen, Zhu Jun Loh, Luo Ping Ger, Forn Chia Lin, Hao Yi Li, Hui Chuan Cheng, Kuen Haur Lee, Michael Hsiao, Pei Jung Lu

Research output: Contribution to journalArticlepeer-review

Abstract

Currently, the survival rate for breast cancer is more than 90%, but once the cancer cells metastasize to distal organs, the survival rate is dramatically reduced, to less than 30%. Triple-negative breast cancer accounts for 15-20% of all breast cancers. Triple-negative breast cancer (TNBC) is associated with poor prognostic and diagnostic outcomes due to the limiting therapeutic strategies, relative to non-TNBC breast cancers. Therefore, the development of targeted therapy for TNBC metastasis remains an urgent issue. In this study, high Carboxyl-terminal modulator protein (CTMP) is significantly associated with recurrence and disease-free survival rate in TNBC patients. Overexpression of CTMP promotes migration and invasion abilities in BT549 cells. Down-regulating of CTMP expression inhibits migration and invasion abilities in MDA-MB-231 cells. In vivo inoculation of high-CTMP cells enhances distant metastasis in mice. The metastasis incidence rate is decreased in mice injected with CTMP-downregulating MDA-MB-231 cells. Gene expression microarray analysis indicates the Akt-dependent pathway is significantly enhanced in CTMP overexpressing cells compared to the parental cells. Blocking Akt activation via Akt inhibitor treatment or co-expression of the dominant-negative form of Akt proteins successfully abolishes the CTMP mediating invasion in TNBC cells. Our findings suggest that CTMP is a potential diagnostic marker for recurrence and poor disease-free survival in TNBC patients. CTMP promotes TNBC metastasis via the Akt-activation-dependent pathway.

Original languageEnglish
JournalCancer Gene Therapy
DOIs
Publication statusAccepted/In press - 2022

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Cancer Research

Fingerprint

Dive into the research topics of 'Carboxyl-terminal modulator protein facilitates tumor metastasis in triple-negative breast cancer'. Together they form a unique fingerprint.

Cite this