CIP2A cooperates with H-Ras to promote epithelial-mesenchymal transition in cervical-cancer progression.

Abstract

The oncoprotein Cancerous Inhibitor of PP2A (CIP2A) has been reported to interact with Protein phosphatase 2 (PP2A) to stabilize c-Myc and prevent its degradation, and high expression levels of CIP2A have been proved to be related to poor clinical outcomes in multiple cancers. Here, we not only proved that the expression of CIP2A is positively correlated with lymph-node metastasis and cervical-cancer progression, but also revealed a close correlation between the protein's expression and the expression levels of two core epithelial-to-mesenchymal transition (EMT) markers, Vimentin and Snail. In addition, we manipulated CIP2A expression to regulate EMT conversion and employed a pull-down assay, mass-spectrometric (MS) peptide sequencing, as well as bilateral co-immunoprecipitation to identify potentially interacting proteins in cervical-cancer cells. In this study, we proposed and successfully proved, for the first time, that CIP2A physically associates with H-Ras, which leads to the activation of the MEK/ERK signaling pathway and promotes EMT and cervical-cancer progression. Based on our observations and prior findings that CIP2A participates in c-Myc regulation, we conjecture that CIP2A may be a potentially promising molecular target for the adoptive therapy of human cancer.

• Authors: Yi Wu, Ting-Ting Gu, Peng-Sheng Zheng
• Journal: Cancer letters (Cancer Lett) Vol. 356 Issue 2 Pt B Pg. 646-55 (Jan 28 2015) ISSN: 1872-7980 [Electronic] Ireland
• PMID: 25458953 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Chemical References

• Autoantigens
• Biomarkers, Tumor
• CIP2A protein, human
• Intracellular Signaling Peptides and Proteins
• Membrane Proteins
• RNA, Messenger
• HRAS protein, human
• Proto-Oncogene Proteins p21(ras)

Topics

• Animals
• Autoantigens (genetics, metabolism)
• Biomarkers, Tumor
• Blotting, Western
• Carcinoma, Squamous Cell (genetics, metabolism, pathology)
• Cell Movement
• Cell Proliferation
• Disease Progression
• Epithelial-Mesenchymal Transition
• Female
• Humans
• Immunoenzyme Techniques
• Immunoprecipitation
• Intracellular Signaling Peptides and Proteins
• Lymphatic Metastasis
• Male
• Membrane Proteins (genetics, metabolism)
• Mice
• Mice, Nude
• Middle Aged
• Neoplasm Grading
• Neoplasm Staging
• Prognosis
• Proto-Oncogene Proteins p21(ras) (genetics, metabolism)
• RNA, Messenger (genetics)
• Real-Time Polymerase Chain Reaction
• Reverse Transcriptase Polymerase Chain Reaction
• Signal Transduction
• Squamous Intraepithelial Lesions of the Cervix (genetics, metabolism, pathology)
• Tumor Cells, Cultured
• Uterine Cervical Neoplasms (genetics, metabolism, pathology)
• Xenograft Model Antitumor Assays