Membrane cholesterol depletion reduces breast tumor cell migration by a mechanism that involves non-canonical Wnt signaling and IL-10 secretion

Abstract

Background: Migration and invasion are hallmarks of cancer cells that allow their dissemination to other tissues. Studying the cellular and molecular basis of cancer cell migration can help us to understand and control cancer metastasis. Many membrane molecules have been described as being involved in tumor cell migration, and among them is cholesterol. Method: In the present study we investigated the role of membrane cholesterol in the migration of breast tumor cells. The human mammary gland/breast epithelial cell line MDA-MB 231 was used and membrane cholesterol was depleted with methyl-β-cyclodextrin (MbCD). Cell migration was measured in a cell-based scratch assay and the involvement of the Wnt signaling was tested using Lef-1/TCF reporter activation in permanently transfected MDA-MB 231 cells. Cell morphology was analyzed using fluorescent phalloidin to label F-actin structures.

ABCA1 overexpression worsens colorectal cancer prognosis by facilitating tumour growth and caveolin‐1‐dependent invasiveness, and these effects can be ameliorated using the BET inhibitor apabetalone

“…The significance of differences between experimental groups was determined by t-test. overexpression could affect the size of raft domains and the composition of the membrane, its fluidity and flexibility, with consequential implications for cell mobility and cell signalling (Guerra et al, 2016). According to the data presented here, before diagnosis, ABCA1 can be considered a high-risk factor that promotes tumour growth and dissemination of the primary lesion.…”

“…Although we did not focus our research on the structure of the plasma membrane, the implications of an increased presence of ABCA1 together with CAV‐1 stabilization on the plasticity of the plasma membrane cannot be ignored. The increased amount of cholesterol in the membrane derived from ABCA 1 overexpression could affect the size of raft domains and the composition of the membrane, its fluidity and flexibility, with consequential implications for cell mobility and cell signalling (Guerra et al ., ). According to the data presented here, before diagnosis, ABCA 1 can be considered a high‐risk factor that promotes tumour growth and dissemination of the primary lesion.…”

ROCK inhibition with Fasudil induces beta-catenin nuclear translocation and inhibits cell migration of MDA-MB 231 human breast cancer cells

“…Perturbation of Wnt signaling with aberrant expression of Wnt factors, their receptors, or downstream signaling molecules may lead to the development of several human cancers 8 . Recently our group demonstrated that the disorganization of cholesterol enriched-lipid rafts leads to Wnt signaling resulting in reduced tumor cells migration 9 .…”

Complex polymorphisms in endocytosis genes suggest alpha-cyclodextrin as a treatment for breast cancer

“…(Li 2006) In particular, MβCD treatment induced a substantial decrease (40%) in activity of breast cancer resistance protein (BCRP/ABCG2), (Storch 2007) which transports PS and PC analogues. (Daleke 2007) In subsequent functional studies, MβCD inhibited spheroid migration and invasion of MDA-MB-241 and ZR751 breast cancer cells (Raghu 2010) and also endocytosis (Palaniyandi 2012) and migration (Guerra 2016b) of MCF7 breast cancer cells. MβCD was more toxic for invasive than for non-invasive urothelial cancer cells, (Resnik 2015) and interfered with RTK-[PI2]-PI3K-[PI3]-AKT signaling in HeLa cells.…”