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

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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.

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Abbreviations

HNSCC:

Head and neck squamous cell carcinoma

OSCC:

Oral squamous cell carcinoma

EGFR:

Epidermal growth factor receptor

HER2:

Human epidermal growth factor receptor 2

MMP-2:

Matrix metalloproteinase-2

MMP-9:

Matrix metalloproteinase-9

RACK1:

Receptor for activated protein kinase C

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Acknowledgments

This work was supported by grants from the National Science Foundation for Distinguished Young Scholars of China (No. 30725041), State Key Program of National Natural Science of China (No. 30930100), the National Natural Science Foundation of China (No. 30901676, 81072218, 30801294), the Science Funds for Talented Professionals of Sichuan Province in China (No. 09ZQ026-037) and the Fok Ying-Tong Education Foundation, China (No. 122030).

Conflict of interest

The authors declare that they have no competing interests.

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Authors and Affiliations

  1. State Key Laboratory of Oral Diseases, West China College of Stomatology, Sichuan University, No. 14, Sec.3, Renminnan Road, Chengdu, 610041, Sichuan, China

    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

  2. Department of Oral Medicine, Guanghua School of Stomatology, Sun Yat-Sen University, No. 56, Lingyuanwest Road, Yuexiu, Guangzhou, 510055, Guangdong, China

    Zhi Wang

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  1. Jing Li
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  2. Yu Guo
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  3. Xiaodong Feng
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  17. Lu Jiang
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Corresponding authors

Correspondence to Lu Jiang or Zhi Wang.

Additional information

Jing Li and Yu Guo contributed equally to this work.

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Li, J., Guo, Y., Feng, X. et al. Receptor for activated C kinase 1 (RACK1): a regulator for migration and invasion in oral squamous cell carcinoma cells. J Cancer Res Clin Oncol 138, 563–571 (2012). https://doi.org/10.1007/s00432-011-1097-7

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  • DOI: https://doi.org/10.1007/s00432-011-1097-7

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