MELK Accelerates the Progression of Colorectal Cancer via Activating the FAK/Src Pathway

Biochem Genet. 2020 Oct;58(5):771-782. doi: 10.1007/s10528-020-09974-x. Epub 2020 May 29.

Abstract

Maternal embryo leucine zipper kinase (MELK) has a higher expression level in a variety of cancers and involved in progression of colorectal cancer. The MELK expression levels in colorectal cancer tissues and cells were detected by RT-qPCR. MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) and transwell assays were used to examine the effect of the MELK konckdown on the proliferation, migration and invasion of colorectal cancer cells. Western blot analysis was used to detect the protein level of MELK and the downstream signaling pathways related proteins. Our findings indicated that MELK expression in colorectal cancer tissues was significantly higher than that in para-carcinoma tissues. Knockdown of MELK with shRNA had strong inhibition effects on the proliferation, migration and invasion of colorectal cancer cells. MELK knockdown could also decrease the phosphorylation level of AKT through FAK/Src pathway. Our results indicated downregulation of MELK retarded the progression of CRC by inhibition of the phosphorylation level of AKT through inactivating FAK/Src pathways. Therefore, MELK has the potential to be explored as a new therapeutic target and knockdown can be used as a potential treatment strategy for colorectal cancer.

Keywords: AKT; Colorectal cancer; FAK/Src pathway; MELK; Proliferation.

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Colorectal Neoplasms / genetics
  • Colorectal Neoplasms / metabolism*
  • Disease Progression
  • Female
  • Focal Adhesion Kinase 1 / metabolism*
  • Gene Expression Regulation, Neoplastic
  • Gene Knockdown Techniques
  • Humans
  • Mice
  • Mice, Nude
  • Phosphorylation
  • Protein Serine-Threonine Kinases / physiology*
  • Proto-Oncogene Proteins c-akt / metabolism
  • Proto-Oncogene Proteins pp60(c-src) / metabolism*
  • Signal Transduction

Substances

  • MELK protein, human
  • Focal Adhesion Kinase 1
  • PTK2 protein, human
  • Proto-Oncogene Proteins pp60(c-src)
  • Protein Serine-Threonine Kinases
  • Proto-Oncogene Proteins c-akt