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

// Yingying Zhu 1, 2, 3, * , Naouel Ailane 1, 2, * , Monica Sala-Valdes 1, 2 , Farhad Haghighi-Rad 1, 2 , Martine Billard 1, 2 , Viet Nguyen 2, 4 , Raphael Saffroy 2, 5, 6 , Antoinette Lemoine 2, 5, 6 , Eric Rubinstein 1, 2 , Claude Boucheix 1, 2 , Celine Greco 1, 2, 7 1 Inserm, UMR-S 935, SFR Andre Lwoff, Villejuif, France 2 Universite Paris-Sud 11, Paris, France 3 Department of Oncology, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, Hubei Province, China 4 Inserm, UMS-33, SFR Andre Lwoff, Villejuif, France 5 Inserm UMR-S 1193, SFR Andre Lwoff, Villejuif, France 6 AP HP, Hopital Paul-Brousse, Department of Biochemistry, Villejuif, France 7 AP HP, Hopital Necker, Department of Pain and Palliative Medicine, Paris, France * These authors have contributed equally to this work Correspondence to: Celine Greco, email: celine.greco@inserm.fr Keywords: Co-029/tspan8, colorectal carcinoma, cell motility, mycoplasmas, EGFR Received: May 20, 2016      Accepted: February 20, 2017      Published: March 16, 2017 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.