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Overexpressions of RACK1 and CD147 Associated with Poor Prognosis in Stage T1 Pulmonary Adenocarcinoma

  • Translational Research and Biomarkers
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Annals of Surgical Oncology Aims and scope Submit manuscript

Abstract

Background

RACK1 has been shown to be able to interact with some key cellular proteins involved in tumor development and progression. Our study showed that the expressions of RACK1 and CD147 are correlated with each other. The purpose of this study is to clarify the relationship between expression of RACK1 and CD147 in 180 patients with operable stage T1 human pulmonary adenocarcinoma and their clinicopathological features and prognostic significance.

Methods

DNA transfection and RNA interference of RACK1 were conducted to produce pulmonary adenocarcinoma cell lines with differential RACK1 expression. Western blot and RT-PCR were used to quantify RACK1 and CD147 expression in protein and mRNA levels in pulmonary adenocarcinoma cell lines. Immunohistochemistry, double-labeling immunofluorescence, confocal laser scanning microscopy, and Western blot were used to correlate the clinicopathological significance of RACK1 and CD147 expression in cases of stage T1 pulmonary adenocarcinoma.

Results

We detected high levels of RACK1 and CD147 mRNA as well as protein expression in pulmonary adenocarcinoma in vitro. In pulmonary adenocarcinoma, the expression of RACK1 and CD147 were correlated both in vitro and in vivo. Our clinicopathological analysis demonstrated that RACK1 or CD147 expression correlated with higher incidence of lymph node metastasis and lower differentiation than tumors that were negative for expression of either RACK1 or CD147. The expression of RACK1 and CD147 was not associated with the patient age or gender. Multivariate analysis demonstrated that the co-overexpression of RACK1 and CD147 was an independent prognostic factor for stage T1 pulmonary adenocarcinoma (P = 0.012).

Conclusions

Tumor invasiveness is associated with expression of RACK1 and CD147 in pulmonary adenocarcinoma. The co-expression of RACK1 and CD147 could be an important prognostic biomarker for stage T1 pulmonary adenocarcinoma.

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References

  1. Mochly-Rosen D, Khaner H, Lopez J. Identification of intracellular receptor proteins for activated protein kinase C. Proc Natl Acad Sci USA. 1991;88:3997–4000.

    Article  PubMed  CAS  Google Scholar 

  2. Zhang W, Zong CS, Hermanto U, Lopez-Bergami P, Ronai Z, Wang LH. RACK1 recruits STAT3 specifically to insulin and insulin-like growth factor 1 receptors for activation, which is important for regulating anchorage-independent growth. Mol Cell Biol. 2006;26:413–24.

    Article  PubMed  CAS  Google Scholar 

  3. Li S, Esterberg R, Lachance V, Ren D, Radde-Gallwitz K, Chi F, et al. Rack1 is required for Vangl2 membrane localization and planar cell polarity signaling while attenuating canonical Wnt activity. Proc Natl Acad Sci USA. 2011;108:2264–9.

    Article  PubMed  CAS  Google Scholar 

  4. Wang F, Yamauchi M, Muramatsu M, Osawa T, Tsuchida R, Shibuya M. RACK1 regulates VEGF/Flt1-mediated cell migration via activation of a PI3 K/Akt pathway. J Biol Chem. 2011;286:9097–106.

    Article  PubMed  CAS  Google Scholar 

  5. Wu Y, Wang Y, Sun Y, Zhang L, Wang D, Ren F, et al. RACK1 promotes Bax oligomerization and dissociates the interaction of Bax and Bcl-XL. Cell Signal. 2010;22:1495–501.

    Article  PubMed  CAS  Google Scholar 

  6. Kiely PA, Baillie GS, Barrett R, Buckley DA, Adams DR, Houslay MD, et al. Phosphorylation of RACK1 on tyrosine 52 by c-Abl is required for insulin-like growth factor I-mediated regulation of focal adhesion kinase. J Biol Chem. 2009;284:20263–74.

    Article  PubMed  CAS  Google Scholar 

  7. Wang Z, Zhang B, Jiang L, Zeng X, Chen Y, Feng X, et al. RACK1, an excellent predictor for poor clinical outcome in oral squamous carcinoma, similar to Ki67. Eur J Cancer. 2009;45:490–6.

    Article  PubMed  CAS  Google Scholar 

  8. He X, Wang J, Messing EM, Wu G. Regulation of receptor for activated C kinase 1 protein by the von Hippel-Lindau tumor suppressor in IGF-I-induced renal carcinoma cell invasiveness. Oncogene. 2011;30:535–47.

    Article  PubMed  CAS  Google Scholar 

  9. Al-Reefy S, Mokbel K. The role of RACK1 as an independent prognostic indicator in human breast cancer. Breast Cancer Res Treat. 2010;123:911.

    Article  PubMed  Google Scholar 

  10. Gabison EE, Hoang-Xuan T, Mauviel A, Menashi S. EMMPRIN/CD147, an MMP modulator in cancer, development and tissue repair. Biochimie. 2005;87:361–8.

    Article  PubMed  CAS  Google Scholar 

  11. Cao XX, Xu JD, Xu JW, Liu XL, Cheng YY, Wang WJ, et al. RACK1 promotes breast carcinoma proliferation and invasion/metastasis in vitro and in vivo. Breast Cancer Res Treat. 2010;123:375–86.

    Article  PubMed  CAS  Google Scholar 

  12. Dai SD, Wang Y, Zhang JY, Zhang D, Zhang PX, Jiang GY, et al. Upregulation of δ-catenin is associated with poor prognosis and enhances transcriptional activity through Kaiso in non-small-cell lung cancer. Cancer Sci. 2011;102:95–103.

    Article  PubMed  CAS  Google Scholar 

  13. Yaka R, Thornton C, Vagts AJ, Phamluong K, Bonci A, Ron D. NMDA receptor function is regulated by the inhibitory scaffolding protein, RACK1. Proc Natl Acad Sci USA. 2002;99:5710–5.

    Article  PubMed  CAS  Google Scholar 

  14. Mourton T, Hellberg CB, Burden-Gulley SM, Hinman J, Rhee A, Brady-Kalnay SM. The PTPmu protein-tyrosine phosphatase binds and recruits the scaffolding protein RACK1 to cell-cell contacts. J Biol Chem. 2001;27:14896–901.

    Article  Google Scholar 

  15. Yarwood SJ, Steele MR, Scotland G, Houslay MD, Bolger GB. The RACK1 signaling scaffold protein selectively interacts with the cAMP-specific phosphodiesterase PDE4D5 isoform. J Biol Chem. 1999;274:14909–17.

    Article  PubMed  CAS  Google Scholar 

  16. Saito A, Fujii G, Sato Y, Gotoh M, Sakamoto M, Toda G, et al. Detection of genes expressed in primary colon cancers by in situ hybridisation: overexpression of RACK 1. Mol Pathol. 2002;55:34–9.

    Article  PubMed  CAS  Google Scholar 

  17. Mamidipudi V, Cartwright CA. A novel pro-apoptotic function of RACK1: suppression of Src activity in the intrinsic and Akt pathways. Oncogene. 2009;28:4421–33.

    Article  PubMed  CAS  Google Scholar 

  18. Nagashio R, Sato Y, Matsumoto T, Kageyama T, Satoh Y, Shinichiro R, et al. Expression of RACK1 is a novel biomarker in pulmonary adenocarcinomas. Lung Cancer. 2010;69:54–9.

    Article  PubMed  Google Scholar 

  19. Guo H, Li R, Zucker S, Toole BP. EMMPRIN (CD147), an inducer of matrix metalloproteinase synthesis, also binds interstitial collagenase to the tumor cell surface. Cancer Res. 2000;60:888–91.

    PubMed  CAS  Google Scholar 

  20. Ishibashi Y, Matsumoto T, Niwa M, Suzuki Y, Omura N, Hanyu N, et al. CD147 and matrix metalloproteinase-2 protein expression as significant prognostic factors in esophageal squamous cell carcinoma. Cancer. 2004;101:1994–2000.

    Article  PubMed  CAS  Google Scholar 

  21. Reimers N, Zafrakas K, Assmann V, Egen C, Riethdorf L, Riethdorf S, et al. Expression of extracellular matrix metalloproteases inducer on micrometastatic and primary mammary carcinoma cells. Clin Cancer Res. 2004;10:3422–8.

    Article  PubMed  CAS  Google Scholar 

  22. Davidson B, Goldberg I, Berner A, Kristensen GB, Reich R. EMMPRIN (extracellular matrix metalloproteinase inducer) is a novel marker of poor outcome in serous ovarian carcinoma. Clin Exp Metastasis. 2003;20:161–9.

    Article  PubMed  CAS  Google Scholar 

  23. Zheng HC, Takahashi H, Murai Y, Cui ZG, Nomoto K, Miwa S, et al. Upregulated EMMPRIN/CD147 might contribute to growth and angiogenesis of gastric carcinoma: a good marker for local invasion and prognosis. Br J Cancer. 2006;95:1371–8.

    Article  PubMed  CAS  Google Scholar 

  24. Sienel W, Polzer B, Elshawi K, Lindner M, Morresi-Hauf A, Vay C, et al. Cellular localization of EMMPRIN predicts prognosis of patients with operable lung adenocarcinoma independent from MMP-2 and MMP-9. Mod Pathol. 2008;21:1130–8.

    Article  PubMed  CAS  Google Scholar 

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Acknowledgment

This study was supported by National Nature Science Foundation of China (No. 30971114).

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Correspondence to Yuchen Han Ph.D.

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Zhong, X., Li, M., Nie, B. et al. Overexpressions of RACK1 and CD147 Associated with Poor Prognosis in Stage T1 Pulmonary Adenocarcinoma. Ann Surg Oncol 20, 1044–1052 (2013). https://doi.org/10.1245/s10434-012-2377-4

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  • DOI: https://doi.org/10.1245/s10434-012-2377-4

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