MAEL expression links epithelial-mesenchymal transition and stem cell properties in colorectal cancer

Int J Cancer. 2016 Dec 1;139(11):2502-11. doi: 10.1002/ijc.30388. Epub 2016 Aug 29.

Abstract

MAEL plays a central role during spermatogenesis by repressing transposable elements and preventing their mobilisation, however, its role on cancers is unclear. In this study, MAEL expression was analysed in a tissue microarray containing 185 samples of primary colon cancer tumor samples and human colon cancer cell lines. The effect of MAEL on cell proliferation, tumorigenesis, metastasis and drug resistance was examined in vitro and in vivo. Immunoprecipitation assay, confocal immunofluorescent analysis and luciferase assay were used for mechanism study. As results, MAEL was significantly upregulated in colon cancer patient tissue samples, and elevated MAEL protein levels positively correlated with overall survival and disease free survival of colon cancer patients. Using in vitro and in vivo models, we demonstrated that MAEL expression was correlated with cell proliferation, invasion and drug resistance of colon cancer cells by inducing epithelial-mesenchymal transition and stemness characteristics. Mechanistically, our study demonstrated that MAEL interacts with Snail and inhibit E-cadherin promoter activity. Collectively, MAEL is an oncogene that plays an important role in the development and progression of colon cancer, which may be a novel potential therapeutic target for colon cancer.

Keywords: MAEL; colorectal cancer; epithelial-mesenchymal transition; stemness.

MeSH terms

  • Animals
  • Antigens, CD
  • Cadherins / metabolism
  • Carrier Proteins / biosynthesis*
  • Carrier Proteins / genetics
  • Cell Line, Tumor
  • Colorectal Neoplasms / genetics
  • Colorectal Neoplasms / metabolism*
  • Colorectal Neoplasms / pathology*
  • DNA-Binding Proteins
  • Epithelial-Mesenchymal Transition
  • HCT116 Cells
  • HT29 Cells
  • Heterografts
  • Humans
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Neoplasm Staging
  • Neoplastic Stem Cells / metabolism*
  • Neoplastic Stem Cells / pathology*
  • Snail Family Transcription Factors / metabolism
  • Transcription Factors

Substances

  • Antigens, CD
  • CDH1 protein, human
  • Cadherins
  • Carrier Proteins
  • DNA-Binding Proteins
  • MAEL protein, human
  • Snail Family Transcription Factors
  • Transcription Factors