Multi-factorial modulation of colorectal carcinoma cells motility – partial coordination by the tetraspanin Co-029/tspan8
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Yingying Zhu1,2,3,*, Naouel Ailane1,2,*, Monica Sala-Valdés1,2, Farhad Haghighi-Rad1,2, Martine Billard1,2, Viet Nguyen2,4, Raphael Saffroy2,5,6, Antoinette Lemoine2,5,6, Eric Rubinstein1,2, Claude Boucheix1,2, Céline Greco1,2,7
1Inserm, UMR-S 935, SFR André Lwoff, Villejuif, France
2Université Paris-Sud 11, Paris, France
3Department of Oncology, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, Hubei Province, China
4Inserm, UMS-33, SFR André Lwoff, Villejuif, France
5Inserm UMR-S 1193, SFR André Lwoff, Villejuif, France
6AP HP, Hôpital Paul-Brousse, Department of Biochemistry, Villejuif, France
7AP HP, Hôpital Necker, Department of Pain and Palliative Medicine, Paris, France
*These authors have contributed equally to this work
Céline Greco, email: firstname.lastname@example.org
Keywords: Co-029/tspan8, colorectal carcinoma, cell motility, mycoplasmas, EGFR
Received: May 20, 2016 Accepted: February 20, 2017 Published: March 16, 2017
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.
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