Increased autophagic response in a population of metastatic breast cancer cells

Abstract

Breast cancer cells are heterogeneous in their ability to invade and fully metastasize, and thus also in their capacity to survive the numerous stresses encountered throughout the multiple steps of the metastatic cascade. Considering the role of autophagy as a survival response to stress, the present study hypothesized that distinct populations of breast cancer cells may possess an altered autophagic capacity that influences their metastatic potential. It was observed that a metastatic breast cancer cell line, MDA-MB-231, that was sensitive to autophagic induction additionally possessed the ability to proliferate following nutrient deprivation. Furthermore, a selected subpopulation of these cells that survived multiple exposures to starvation conditions demonstrated a heightened response to autophagic induction compared to their parent cells. Although this subpopulation maintained a more grape-like pattern in three-dimensional culture compared to the extended spikes of the parent population, autophagic induction in this subpopulation elicited an invasive phenotype with extended spikes. Taken together, these results suggest that autophagic induction may contribute to the ability of distinct breast cancer cell populations to survive and invade.

Autophagy, Cell Viability, and Chemoresistance Are Regulated By miR-489 in Breast Cancer

“…We selected MDA-MB-231 cells for this study as previous study has showed that MDA-MB-231 cells are more resistant to starvation compared to other breast cancer cell lines. Study also showed that this aggressive cell line is sensitive to autophagic induction and additionally possesses the ability to proliferate following nutrient deprivation (21). Consistent with this study we also observed that MDA-MB-231 cells were much more resistant to starvation compared to T47D and HCC1954 cells.…”

“…Intriguingly, we observed significant cytotoxic effect of miR-489 in TNBC cells compared to cell lines of other breast cancer subtypes. TNBC cell line MDA-MB-231 is sensitive to autophagic induction and additionally possesses the ability to proliferate following nutrient deprivation (21). In the current study, we also observed MDA-MB-231 cells are more resistant to starvation compared to estrogen positive T47D cell line and HER2 positive HCC1954 cell line.…”

ATG5: A central autophagy regulator implicated in various human diseases

“…11 However, autophagy is regulated and acts as a prosurvival process in response to various stimuli such as pathogen invasion, nutrient deprivation/ amino acid starvation, mitochondrial dysfunction, oxidative stress, growth factor withdrawal, and immune cell activation. 12 Autophagy plays a significant role in several human diseases such as cancer, 13 cardiomyopathies, 14,15 neurodegenerative disorders, 16 infectious diseases [17][18][19][20] and pancreatitis, 21 asthma, 22 dental diseases, 23 amyotrophic lateral sclerosis, 24 skin disorders, 25 hereditary spastic paraparesis, 26 and Paget's disease of bone. 27 Autophagy is a central biological mechanism, which drives a broad range of human physiological and pathological conditions.…”