Dual knockdown of Galectin-8 and its glycosylated ligand, the activated leukocyte cell adhesion molecule (ALCAM/CD166), synergistically delays in vivo breast cancer growth.

FERRAGUT, FÁTIMA; SANCHEZ TERRERO, CLARA; VANZULLI, S.I.; CAGNONI, ALEJANDRO J.; ELOLA, MARÍA TERESA; WOLFENSTEIN-TODEL, CARLOTA; COLOMBO, LUCAS L.; RABINOVICH, GABRIEL A.; TRONCOSO, MARÍA F.; MARIÑO, KARINA V.

BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH

ELSEVIER SCIENCE BV

Lugar: Amsterdam; Año: 2019 p. 1338 - 1352

0167-4889

Galectin-8 (Gal-8), a ?tandem-repeat?-type galectin, has been described as a modulator ofcellular functions including adhesion, spreading, growth arrest, apoptosis, pathogen recognition,autophagy, and immunomodulation. We have previously shown that activated leukocyte celladhesion molecule (ALCAM), also known as CD166, serves as a receptor for endogenous Gal-8.ALCAM is a member of the immunoglobulin superfamily involved in cell-cell adhesion throughhomophilic (ALCAM-ALCAM) and heterophilic (i.e. ALCAM-CD6) interactions in differenttissues. Here we investigated the physiologic relevance of ALCAM-Gal-8 association andglycosylation-dependent mechanisms governing these interactions. We found that silencing ofALCAM in MDA-MB-231 triple negative breast cancer cells decreases cell adhesion andmigration onto Gal-8-coated surfaces in a glycan-dependent fashion. Remarkably, either Gal-8 orALCAM silencing also disrupted cell-cell adhesion, and led to reduced tumor growth in a murinemodel of triple negative breast cancer. Moreover, structural characterization of endogenousALCAM N-glycosylation showed abundant permissive structures for Gal-8 binding. Importantly,we also found that cell sialylation controls Gal-8-mediated cell adhesion. Altogether, thesefindings demonstrate a central role of either ALCAM or Gal-8 (or both) in controlling triplenegative breast cancer.