Lectin from Sambucus sieboldiana abrogates the anoikis resistance of colon cancer cells conferred by N-acetylglucosaminyltransferase V during hematogenous metastasis

Oncotarget. 2017 Jun 27;8(26):42238-42251. doi: 10.18632/oncotarget.15034.

Abstract

Anoikis is a form of anchorage-dependent apoptosis, and cancer cells adopt anokis-resistance molecular machinery to conduct metastasis. Here, we report that N-acetylglucosaminyltransferase V gene expression confers anoikis resistance during cancer progression. Overexpression of N-acetylglucosaminyltransferase V protected detached cancer cells from apoptotic death, and suppression or knockout of the gene sensitized cancer cells to the apoptotic death. The gene expression also stimulated anchorage-dependent as well as anchorage-independent colony formation of cancer cells following anoikis stress treatments. Importantly, treatment with the lectin from Sambucus sieboldiana significantly sensitized anoikis-induced cancer cell deaths in vitro as well as in vivo. We propose that the lectin alone or an engineered form could offer a new therapeutic treatment option for cancer patients with advanced tumors.

Keywords: MGAT5; SSA; anoikis; metastasis.

MeSH terms

  • Animals
  • Anoikis / drug effects*
  • Anoikis / genetics
  • Apoptosis / drug effects
  • Apoptosis / genetics
  • Cell Line, Tumor
  • Cell Proliferation
  • Colonic Neoplasms / genetics
  • Colonic Neoplasms / metabolism*
  • Colonic Neoplasms / pathology*
  • Disease Models, Animal
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic
  • Gene Knockout Techniques
  • Humans
  • Mice
  • N-Acetylglucosaminyltransferases / genetics
  • N-Acetylglucosaminyltransferases / metabolism*
  • Neoplasm Metastasis
  • Plant Lectins / pharmacology*
  • Sambucus / chemistry*
  • Transcriptome
  • Xenograft Model Antitumor Assays

Substances

  • Plant Lectins
  • N-Acetylglucosaminyltransferases
  • alpha-1,6-mannosylglycoprotein beta 1,6-N-acetylglucosaminyltransferase