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Down-regulation of SNX1 predicts poor prognosis and contributes to drug resistance in colorectal cancer

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Tumor Biology

Abstract

As a potential tumor suppressor, the detailed clinical application value of sorting nexin 1 (SNX1) has not been elucidated in colorectal cancer (CRC). The aim of the present study was to evaluate the expression of SNX1 in CRC tissues and to determine its correlation with clinicopathologic characteristics and its impact on patient’s prognosis. We detected the expression of SNX1 mRNA in 72 CRC patients and SNX1 protein in 237 CRC patients by real-time polymerase chain reaction (RT-PCR) and immunohistochemical staining, respectively. Relationship between the expression of SNX1 and various clinicopathological features in these patients was evaluated. Both the mRNA and protein expression of SNX1 were remarkably decreased in CRC tissues compared with paired non-cancerous tissues, and the down-regulation of SNX1 protein was strongly associated with poor differentiation and poor overall survival (OS) rate of CRC patients. Ectopic SNX1 expression repressed CRC cell growth and promoted tumor sensitivity to most commonly used chemotherapeutic drugs (oxaliplatin and 5-Fluorouracil). In conclusion, overexpression of SNX1 may serve as a new therapeutic strategy for CRC.

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References

  1. Torre LA, Bray F, Siegel RL, et al. Global cancer statistics, 2012. CA Cancer J Clin. 2015;65:87–108.

    Article  PubMed  Google Scholar 

  2. Cerella C, Teiten MH, Radogna F, et al. From nature to bedside: pro-survival and cell death mechanisms as therapeutic targets in cancer treatment. Biotechnol Adv. 2014;32:1111–22.

    Article  CAS  PubMed  Google Scholar 

  3. Nguyen LN, Holdren MS, Nguyen AP, et al. Sorting nexin 1 down-regulation promotes colon tumorigenesis. Clin Cancer Res. 2006;12:6952–9.

    Article  CAS  PubMed  Google Scholar 

  4. Huang Z, Huang S, Wang Q, et al. MicroRNA-95 promotes cell proliferation and targets sorting Nexin 1 in human colorectal carcinoma. Cancer Res. 2011;71:2582–9.

    Article  CAS  PubMed  Google Scholar 

  5. Chen X, Chen S, Hang W, et al. MiR-95 induces proliferation and chemo- or radioresistance through directly targeting sorting nexin1 (SNX1) in non-small cell lung cancer. Biomed Pharmacother. 2014;68:589–95.

    Article  CAS  PubMed  Google Scholar 

  6. Nishimura Y, Takiguchi S, Ito S, et al. EGF-stimulated AKT activation is mediated by EGFR recycling via an early endocytic pathway in a gefitinib-resistant human lung cancer cell line. Int J Oncol. 2015;46:1721–9.

    CAS  PubMed  Google Scholar 

  7. Centelles JJ. General aspects of colorectal cancer. ISRN Oncol. 2012;2012:139268.

    PubMed  PubMed Central  Google Scholar 

  8. Osman I, Bajorin DF, Sun TT, et al. Novel blood biomarkers of human urinary bladder cancer. Clin Cancer Res. 2006;12:3374–80.

    Article  CAS  PubMed  Google Scholar 

  9. Gullapalli A, Wolfe BL, Griffin CT, et al. An essential role for SNX1 in lysosomal sorting of protease-activated receptor-1: evidence for retromer-, Hrs-, and Tsg101-independent functions of sorting nexins. Mol Biol Cell. 2006;17:1228–38.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Worby CA, Dixon JE. Sorting out the cellular functions of sorting nexins. Nat Rev Mol Cell Biol. 2002;3:919–31.

    Article  CAS  PubMed  Google Scholar 

  11. Ernst T, Score J, Deininger M, et al. Identification of FOXP1 and SNX2 as novel ABL1 fusion partners in acute lymphoblastic leukaemia. Br J Haematol. 2011;153:43–6.

    Article  CAS  PubMed  Google Scholar 

  12. Ara S, Kikuchi T, Matsumiya H, et al. Sorting nexin 5 of a new diagnostic marker of papillary thyroid carcinoma regulates Caspase-2. Cancer Sci. 2012;103:1356–62.

    Article  CAS  PubMed  Google Scholar 

  13. Rivera J, Megias D, Bravo J. Sorting nexin 6 interacts with breast cancer metastasis suppressor-1 and promotes transcriptional repression. J Cell Biochem. 2010;111:1464–72.

    Article  CAS  PubMed  Google Scholar 

  14. Panczyk M. Pharmacogenetics research on chemotherapy resistance in colorectal cancer over the last 20 years. World J Gastroenterol. 2014;20:9775–827.

    Article  PubMed  PubMed Central  Google Scholar 

  15. Kerr JF, Winterford CM, Harmon BV. Apoptosis. Its significance in cancer and cancer therapy. Cancer. 1994;73:2013–26.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This study was partially supported by grants from the National Natural Science Foundation of China (Nos. 81000867, 81272299, 81301920 and 81301784) and Medical Key Professionals Program of Jiangsu Province (RC2011031).

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Authors and Affiliations

  1. Wuxi Oncology Institute, The Affiliated Hospital of Jiangnan University, 200 Huihe Road, Wuxi, Jiangsu, 214062, China

    Zehua Bian, Yuyang Feng, Yao Xue, Yaling Hu, Leyuan Zhou, Zhihui Liu, Jiwei Zhang, Yuan Yin & Zhaohui Huang

  2. Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, 200032, China

    Qifeng Wang

  3. Department of Laboratory Medicine, Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu, 221002, China

    Bing Gu

  4. Medical Technology Institute of Xuzhou Medical College, Xuzhou, Jiangsu, 221002, China

    Bing Gu

Authors
  1. Zehua Bian
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  2. Yuyang Feng
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  3. Yao Xue
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  4. Yaling Hu
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  5. Qifeng Wang
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  6. Leyuan Zhou
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  7. Zhihui Liu
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  8. Jiwei Zhang
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  9. Yuan Yin
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  10. Bing Gu
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  11. Zhaohui Huang
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Corresponding author

Correspondence to Zhaohui Huang.

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Bian, Z., Feng, Y., Xue, Y. et al. Down-regulation of SNX1 predicts poor prognosis and contributes to drug resistance in colorectal cancer. Tumor Biol. 37, 6619–6625 (2016). https://doi.org/10.1007/s13277-015-3814-3

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  • DOI: https://doi.org/10.1007/s13277-015-3814-3

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