EXPLORING THE LINKS: CANCER STEM CELLS, TGF-β PATHWAY, AND GPC3

MARTINEZ GOMEZ, MAIA JAZMÍN; ARIZA BAREÑO, LIZETH AIXA; BRITEZ NEIRA, DIEGO JAVIER; PETERS, MARÍA GISELLE

Mar del Plata, Buenos Aires

Congreso; REUNIÓN DE SOCIEDADES DE BIOCIENCIAS 2023; 2023

Sociedad Argentina de Investigación Clínica

We have demonstrated that GPC3 expression reverses the epithelial-to-mesenchymal transition (EMT) undergone by breast cancer cells. Given the role of the TGF-β pathway in this process, and reports indicating that the EMT confers stem-like attributes, we decided to analyze the putative relation among GPC3, TGF-β, and stem cells. To analyze the impact of GPC3 on the stem cell population, we evaluated the ability to form mammospheres of breast cancer cells with genetically modified GPC3 expression. GPC3 overexpression increased MDA-MB231 sphere formation by about 15%, and its silencing in MCF-7 cells reduced it by 45%. While control MDA-MB231 spheres were like “clusters”, GPC3-overexpressing ones were large with cells concentrically arranged. qPCR assays showed that NANOG and OCT4 were poorly expressed in cell monolayers, but in silico studies exhibited upregulation of stem markers such as SOX, ALDH1A1, and KLF4, in human mammary tumors defined as “high GPC3” (FDR0,5). Using the TCGA database, the gene enrichment analysis proved that several signatures involved in the stem regulation are upregulated in patients with “high GPC3” (as GOBP_STEM_CELL_PROLIFERATION, FDR