Up-regulation of SLC9A9 Promotes Cancer Progression and Is Involved in Poor Prognosis in Colorectal Cancer

Anticancer Res. 2017 May;37(5):2255-2263. doi: 10.21873/anticanres.11562.

Abstract

Background/aim: SLC9A9 plays an oncogenic role in esophageal squamous carcinoma and glioblastoma. Herein, we showed an oncogenic function of SLC9A9 in colorectal cancer (CRC).

Materials and methods: We examined SLC9A9 expression in CRC specimens by immunohistochemistry. In CRC tissues, the relationship between SLC9A9 expression and clinicopathological factors was further elucidated by quantitative real-time polymerase chain reaction (qRT-PCR) and gene set enrichment analysis (GSEA). In vitro, we performed knockdown and overexpression experiments.

Results: SLC9A9 was overexpressed in CRC specimens. In clinicopathological analysis of our cohort, high SLC9A9 expression increased liver metastasis and was correlated with worse prognoses in two cohorts. A significantly positive relationship between SLC9A9 and EGFR was revealed. While knockdown of SLC9A9 suppressed proliferation and anchorage-independent growth, up-regulation of SLC9A9 promoted proliferation and anchorage-independent growth in vitro.

Conclusion: SLC9A9 has an oncogenic function by being related to EGFR signaling, suggesting SLC9A9 may be a novel prognostic indicator and a therapeutic target in CRC.

Keywords: EGFR; SLC9A9; colorectal cancer; prognosis.

MeSH terms

  • Aged
  • Cell Line, Tumor
  • Colorectal Neoplasms / genetics
  • Colorectal Neoplasms / metabolism*
  • Colorectal Neoplasms / pathology
  • Disease Progression
  • ErbB Receptors / genetics
  • ErbB Receptors / metabolism*
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Male
  • Prognosis
  • RNA, Messenger / genetics
  • RNA, Small Interfering / genetics
  • Sodium-Hydrogen Exchangers / genetics
  • Sodium-Hydrogen Exchangers / metabolism*
  • Up-Regulation

Substances

  • RNA, Messenger
  • RNA, Small Interfering
  • SLC9A9 protein, human
  • Sodium-Hydrogen Exchangers
  • EGFR protein, human
  • ErbB Receptors