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.
Sorting nexin 1 (SNX1) Colorectal cancer (CRC) Prognosis Drug resistance
This is a preview of subscription content, log in to check access.
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).
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.CrossRefPubMedGoogle Scholar
Nguyen LN, Holdren MS, Nguyen AP, et al. Sorting nexin 1 down-regulation promotes colon tumorigenesis. Clin Cancer Res. 2006;12:6952–9.CrossRefPubMedGoogle Scholar
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.CrossRefPubMedGoogle Scholar
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.CrossRefPubMedGoogle Scholar
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.PubMedGoogle Scholar
Osman I, Bajorin DF, Sun TT, et al. Novel blood biomarkers of human urinary bladder cancer. Clin Cancer Res. 2006;12:3374–80.CrossRefPubMedGoogle Scholar
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.CrossRefPubMedPubMedCentralGoogle Scholar