Receptor for activated C kinase 1 (RACK1): a regulator for migration and invasion in oral squamous cell carcinoma cells.

Abstract

PURPOSE:

Receptor of activated protein kinase C 1 (RACK1) has been identified as an anchoring or adaptor protein in multiple intracellular signal transduction pathways. Our previous study has showed that the expression of RACK1 was paralleled with proliferation and correlated with metastasis and clinical outcome. However, the underlined mechanism has not been uncovered.

MATERIALS AND METHODS:

We first selected a most effective siRNA among three siRNAs (siRNA-1, siRNA-2 and siRNA-3) targeting different regions in the RACK1 mRNA and re-evaluated the anticancer effect of RACK1 silencing on HSC-3 and Cal-27 cell lines by cell growth inhibition. And then, we investigated whether knockdown of RACK1 could inhibit cell adhesion, migration and invasion in these two cell lines. To further understand the molecular mechanism of RACK1 in these processes, the expressions of EGFR, pEGFR, HER2, MMP-2 and MMP-9 were detected by western blot.

RESULTS:

We verified that the silence of RACK1 gene in two OSCC cell lines could not only inhibit cell proliferation but also decrease the invasion, migration and adhesion capability of the tumor cells. Further, western blot analysis deduced that it might be related to the decrease in protein expression of EGFR, pEGFR, HER2, MMP-2 and MMP-9.

CONCLUSION:

Our results clearly showed the significance of RACK1-induced OSCC cell migration, invasion and adhesion, which could explain the underlined mechanism of the effect of the gene on metastasis and clinical outcome. Also, our results confirmed its role to be a prognostic indicator and a promising drug target for OSCC cell metastasis.

• Authors: Jing Li, Yu Guo, Xiaodong Feng, Zhiyong Wang, Yun Wang, Peng Deng, Dunfang Zhang, Ruinan Wang, Liang Xie, Xiaoping Xu, Yu Zhou, Ning Ji, Jing Hu, Min Zhou, Ga Liao, Ning Geng, Lu Jiang, Zhi Wang, Qianming Chen
• Journal: Journal of cancer research and clinical oncology (J Cancer Res Clin Oncol) Vol. 138 Issue 4 Pg. 563-71 (Apr 2012) ISSN: 1432-1335 [Electronic] Germany
• PMID: 22207523 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Neoplasm Proteins
• RACK1 protein, human
• Receptors for Activated C Kinase
• Receptors, Cell Surface
• EGFR protein, human
• ERBB2 protein, human
• ErbB Receptors
• Receptor, ErbB-2
• MMP2 protein, human
• Matrix Metalloproteinase 2
• Matrix Metalloproteinase 9
• GTP-Binding Proteins

Topics

• Blotting, Western
• Carcinoma, Squamous Cell (genetics, metabolism)
• Cell Adhesion
• Cell Line, Tumor
• Cell Movement (genetics, physiology)
• Cell Proliferation
• ErbB Receptors (metabolism)
• GTP-Binding Proteins (genetics, metabolism, physiology)
• Gene Expression Regulation, Neoplastic
• Humans
• Matrix Metalloproteinase 2 (metabolism)
• Matrix Metalloproteinase 9 (metabolism)
• Mouth Neoplasms (genetics, metabolism, pathology)
• Neoplasm Invasiveness
• Neoplasm Proteins (genetics, metabolism, physiology)
• RNA Interference
• Receptor, ErbB-2 (metabolism)
• Receptors for Activated C Kinase
• Receptors, Cell Surface (genetics, metabolism, physiology)
• Reverse Transcriptase Polymerase Chain Reaction
• Time Factors