IBP regulates epithelial-to-mesenchymal transition and the motility of breast cancer cells via Rac1, RhoA and Cdc42 signaling pathways.

Abstract

Epithelial-to-mesenchymal transition (EMT) is a crucial process for the invasion and metastasis of epithelial tumors. However, the molecular mechanisms underlying this transition are poorly understood. In this study, we demonstrate that interferon regulatory factor 4 binding protein (IBP) regulates EMT and the motility of breast cancer cells through Rac1, RhoA and Cdc42 signaling pathways. We found that increased expression of IBP was associated with the progression of breast cancer and that IBP protein levels were significantly elevated in matched distant metastases. High IBP levels also predict shorter overall survival of breast cancer patients. Furthermore, the forced expression of IBP decreased the expression of the epithelial marker E-cadherin but increased the mesenchymal markers in breast cancer cells. In contrast, silencing IBP in metastatic breast tumor cells promoted a shift toward an epithelial morphology concomitant with increased expression of E-cadherin and decreased expression of mesenchymal markers. IBP silencing also reduced the expression of EMT-inducing transcription factors (Snail, Slug, ZEB1 and ZEB2). Moreover, we identified a role for IBP in endogenous EMT induced by epidermal growth factor (EGF) and deletion of IBP attenuated EGF receptor (EGFR) signaling in breast cancer cells. Furthermore, IBP regulates the migration, invasion and matrix metalloprotease production in breast cancer cells as well as actin cytoskeleton rearrangement and the activation of GTP-Rac1, GTP-RhoA and GTP-Cdc42. Taken together, our findings demonstrate an oncogenic property for IBP in promoting the metastatic potential of breast cancer cells.

• Authors: Z Zhang, M Yang, R Chen, W Su, P Li, S Chen, Z Chen, A Chen, S Li, C Hu
• Journal: Oncogene (Oncogene) Vol. 33 Issue 26 Pg. 3374-82 (Jun 26 2014) ISSN: 1476-5594 [Electronic] England
• PMID: 23975422 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cadherins
• Homeodomain Proteins
• Interferon Regulatory Factors
• RAC1 protein, human
• RNA, Small Interfering
• Repressor Proteins
• SNAI1 protein, human
• Snail Family Transcription Factors
• Transcription Factors
• ZEB1 protein, human
• ZEB2 protein, human
• Zinc Finger E-box Binding Homeobox 2
• Zinc Finger E-box-Binding Homeobox 1
• interferon regulatory factor-4
• RHOA protein, human
• Epidermal Growth Factor
• EGFR protein, human
• ErbB Receptors
• cdc42 GTP-Binding Protein
• rac1 GTP-Binding Protein
• rhoA GTP-Binding Protein

Topics

• Breast Neoplasms (pathology)
• Cadherins (biosynthesis)
• Cell Line, Tumor
• Cell Movement
• Epidermal Growth Factor (metabolism)
• Epithelial-Mesenchymal Transition
• ErbB Receptors (metabolism)
• Female
• Homeodomain Proteins (biosynthesis)
• Humans
• Interferon Regulatory Factors (biosynthesis, genetics, metabolism)
• Neoplasm Invasiveness
• Neoplasm Metastasis (pathology)
• RNA Interference
• RNA, Small Interfering
• Repressor Proteins (biosynthesis)
• Signal Transduction
• Snail Family Transcription Factors
• Transcription Factors (biosynthesis)
• Zinc Finger E-box Binding Homeobox 2
• Zinc Finger E-box-Binding Homeobox 1
• cdc42 GTP-Binding Protein (biosynthesis)
• rac1 GTP-Binding Protein (biosynthesis)
• rhoA GTP-Binding Protein (biosynthesis)