info:eu-repo/semantics/article
Dual knockdown of Galectin-8 and its glycosylated ligand, the activated leukocyte cell adhesion molecule (ALCAM/CD166), synergistically delays in vivo breast cancer growth
Fecha
2019-03-21Registro en:
Ferragut, Fatima Eneida del Valle; Cagnoni, Alejandro; Colombo, Lucas Luis; Sánchez Terrero, Clara; Wolfenstein Todel, Carlota; et al.; Dual knockdown of Galectin-8 and its glycosylated ligand, the activated leukocyte cell adhesion molecule (ALCAM/CD166), synergistically delays in vivo breast cancer growth; Elsevier Science; Biochimica et Biophysica Acta-Molecular Cell Research; 1866; 8; 21-3-2019; 1338-1352
0167-4889
CONICET Digital
CONICET
Autor
Ferragut, Fatima Eneida del Valle
Cagnoni, Alejandro
Colombo, Lucas Luis
Sánchez Terrero, Clara
Wolfenstein Todel, Carlota
Troncoso, María Fernanda
Vanzulli, Silvia
Rabinovich, Gabriel Adrián
Mariño, Karina Valeria
Elola, Maria Teresa
Resumen
Galectin-8 (Gal-8), a ‘tandem-repeat’-type galectin, has been described as a modulator of cellular functions including adhesion, spreading, growth arrest, apoptosis, pathogen recognition, autophagy, and immunomodulation. We have previously shown that activated leukocyte cell adhesion 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 through homophilic (ALCAM-ALCAM) and heterophilic (i.e. ALCAM-CD6) interactions in different tissues. Here we investigated the physiologic relevance of ALCAM-Gal-8 association and glycosylation-dependent mechanisms governing these interactions. We found that silencing of ALCAM in MDA-MB-231 triple negative breast cancer cells decreases cell adhesion and migration onto Gal-8-coated surfaces in a glycan-dependent fashion. Remarkably, either Gal-8 or ALCAM silencing also disrupted cell-cell adhesion, and led to reduced tumor growth in a murine model of triple negative breast cancer. Moreover, structural characterization of endogenous ALCAM N-glycosylation showed abundant permissive structures for Gal-8 binding. Importantly, we also found that cell sialylation controls Gal-8-mediated cell adhesion. Altogether, these findings demonstrate a central role of either ALCAM or Gal-8 (or both) in controlling triple negative breast cancer.