Multi-factorial modulation of colorectal carcinoma cells motility - partial coordination by the tetraspanin Co-029/tspan8

Oncotarget. 2017 Apr 18;8(16):27454-27470. doi: 10.18632/oncotarget.16247.

Abstract

Colorectal carcinoma cells Isreco1 display an ability to migrate controlled by a complex set of signals issued from the membrane. By comparing cells infected by mycoplasmas and mycoplasmas free cells, we have established that basal 2D migration is dependent on a double signal mediated by the collagen receptors integrins alpha1/2 and the Toll-Like receptor TLR2. The signal issued from mycoplasmas can be replaced by a TLR2 ligand and the functional effect is neutralized by silencing of MyD88. Following previous observation that downregulation of E-cadherin/p120 catenin increases cell motility, we now report that EGFR or CD44 inhibition have a similar effect on cell motility that is restricted to tetraspanin Co-029/tspan8 transduced IsrecoI cells (Is1-Co029). The modulation of cell migration linked to EGFR or CD44 can be neutralized by antagonizing Co-029 with the mAb Ts29.1 or by RNA interference. Altogether these data point to a crucial role of Co-029 in the modulation of colon cancer cell motility which could be related to the protumoral effect reported for this tetraspanin. Among surface molecules able to mediate Co-029 function, E-cadherin, EGFR and CD44 appear as likely candidates.

Keywords: Co-029/tspan8; EGFR; cell motility; colorectal carcinoma; mycoplasmas.

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Cell Movement / genetics*
  • Colorectal Neoplasms / genetics
  • Colorectal Neoplasms / metabolism
  • Colorectal Neoplasms / pathology
  • Disease Models, Animal
  • Epithelial-Mesenchymal Transition / genetics
  • ErbB Receptors
  • Heterografts
  • Humans
  • Hyaluronan Receptors / metabolism
  • Mice
  • Multiprotein Complexes / metabolism
  • Mycoplasma
  • Protein Binding
  • Signal Transduction
  • Tetraspanins / genetics*
  • Tetraspanins / metabolism
  • Toll-Like Receptor 2 / metabolism

Substances

  • Hyaluronan Receptors
  • Multiprotein Complexes
  • TSPAN8 protein, human
  • Tetraspanins
  • Toll-Like Receptor 2
  • ErbB Receptors