Syndecan-2 in colorectal cancer plays oncogenic role via epithelial-mesenchymal transition and MAPK pathway

Biomed Pharmacother. 2020 Jan:121:109630. doi: 10.1016/j.biopha.2019.109630. Epub 2019 Nov 7.

Abstract

Purpose: In this study, we aimed to elucidate the biological roles of Syndecan-2 (SDC2) in colorectal cancer (CRC), thereby further understanding its clinical role.

Methods: The expression of SDC2 was assessed by qRT-PCR and Western blot analysis. To understand the potential biological role of SDC2, we also explored the correlation between its expression level and clinicopathologic parameters. By using MTT, plate colony formation assay, Transwell invasion assays, and flow cytometry in vitro, the biological impact of SDC2 on CRC cell proliferation, migration, invasion, and apoptosis. In addition, the related signaling pathways were investigated.

Results: SDC2 expression was significantly upregulated in CRC tissues. The expression of SDC2 was highly associated with four parameters, i.e., stage (P < 0.01), vascular invasion (P = 0.0045), lymph node metastasis (P=0.0018), and distant metastasis (P = 0.0019). Knockdown of SDC2 significantly reduced proliferation, migration, and invasion of HCT116 and SW480 cells, and induced cell apoptosis. Moreover, SDC2 promoted epithelial-mesenchymal transition (EMT) in CRC cells, whereas the ratio of p-MEK/MEK and p-ERK/ERK markedly reduced after depleting SDC2.

Conclusion: During CRC development, overexpression of SDC2 plays a carcinogenic role in CRC. Therapeutic solutions targeting SDC2 may provide potential insights into CRC prevention and treatment.

Keywords: Colorectal cancer; Epithelial-mesenchymal transition; Invasion; Proliferation; Syndecan-2.

MeSH terms

  • Adult
  • Aged
  • Apoptosis
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Colorectal Neoplasms / etiology*
  • Colorectal Neoplasms / pathology
  • Epithelial-Mesenchymal Transition*
  • Female
  • Humans
  • MAP Kinase Signaling System / physiology*
  • Male
  • Middle Aged
  • Neoplasm Invasiveness
  • Syndecan-2 / physiology*

Substances

  • SDC2 protein, human
  • Syndecan-2