SRGN Promotes Colorectal Cancer Metastasis as a Critical Downstream Target of HIF-1α

Cell Physiol Biochem. 2018;48(6):2429-2440. doi: 10.1159/000492657. Epub 2018 Aug 17.


Background/aims: The chondroitin sulfate proteoglycan serglycin (SRGN), a hematopoietic cell granule proteoglycan, has been implicated in promoting tumor metastasis; however, the underlying mechanisms remain to be elucidated. The present study aimed to investigate the SRGN gene expression and its regulation as downstream signaling of hypoxia-inducible transcription factor 1 alpha (HIF-1α) in colorectal cancer (CRC) cells and tissues.

Methods: The expression of SRGN was analyzed in CRC specimens for its correlation with progression and metastasis. Using chromatin-immunoprecipitation (ChIP), quantitative real-time PCR, Western blot, and transwell assay, the functional role and underlying mechanism of SRGN in CRC metastasis were elucidated. Thus, this study provides evidence of a critical role of SRGN in metastatic progression of CRC.

Results: Our results indicated that SRGN overexpression was significantly associated with poor prognosis in CRC specimens. SRGN overexpression promoted CRC cell migration and invasion in vitro; however, SRGN depletion exhibited contrasting effects. Mechanistic investigations revealed that HIF-1α regulated SRGN transcription via physically binding to a hypoxia response element in its promoter region.

Conclusions: In conclusion, we demonstrated that dysregulated HIF-1α/SRGN signaling promotes CRC progression and metastasis. SRGN may serve as a potential candidate therapeutic target for metastatic CRC.

Keywords: Colorectal cancer; EMT; HIF1α; Invasion; Metastasis; Srgn.

MeSH terms

  • Aged
  • Cell Hypoxia
  • Cell Line, Tumor
  • Cell Movement
  • Colorectal Neoplasms / metabolism
  • Colorectal Neoplasms / mortality
  • Colorectal Neoplasms / pathology*
  • Epithelial-Mesenchymal Transition
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Hypoxia-Inducible Factor 1, alpha Subunit / antagonists & inhibitors
  • Hypoxia-Inducible Factor 1, alpha Subunit / genetics
  • Hypoxia-Inducible Factor 1, alpha Subunit / metabolism*
  • Male
  • Middle Aged
  • Prognosis
  • Promoter Regions, Genetic
  • Protein Binding
  • Proteoglycans / antagonists & inhibitors
  • Proteoglycans / genetics
  • Proteoglycans / metabolism*
  • RNA Interference
  • RNA, Small Interfering / metabolism
  • Signal Transduction
  • Survival Rate
  • Vesicular Transport Proteins / antagonists & inhibitors
  • Vesicular Transport Proteins / genetics
  • Vesicular Transport Proteins / metabolism*


  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Proteoglycans
  • RNA, Small Interfering
  • Vesicular Transport Proteins
  • serglycin