Autophagy Supports Breast Cancer Stem Cell Maintenance by Regulating IL6 Secretion

Abstract

Autophagy is a mechanism by which cells degrade cellular material to provide nutrients and energy for survival during stress. The autophagy is thought to be a critical process for cancer stem (CSC) or tumor initiating cell maintenance but the mechanisms by which autophagy supports survival of CSCs remain poorly understood. In this study, inhibition of autophagy by knockdown of ATG7 or BECN1 modified the CD44+/CD24low/− population in breast cancer cells by regulating CD24 and IL6 secretion. In a breast cancer cell line that is independent of autophagy for survival, autophagy inhibition increased IL6 secretion to the media. On the other hand, in an autophagy-dependent cell line, autophagy inhibition decreased IL6 secretion, cell survival and mammosphere formation. In these cells, IL6 treatment or conditioned media from autophagy-competent cells rescued the deficiency in mammosphere formation induced by autophagy inhibition. These results reveal that autophagy regulates breast CSC maintenance in autophagy-dependent breast cancer cells by modulating IL6 secretion implicating autophagy as a potential therapeutic target in breast cancer.

Autophagy Differentially Regulates Distinct Breast Cancer Stem-like Cells in Murine Models via EGFR/Stat3 and Tgfβ/Smad Signaling

“…In further support of the different characteristics of the ALDH + and CD29 hi CD61 + BCSCs, we found that while it affected both BCSCs, which is consistent with a number of previous reports (20,21,40), inhibition of autophagy by FIP200 deletion compromised ALDH + and CD29 hi CD61 + BCSCs through defects in the Stat3 and TGF-β/Smad pathways, respectively. Regulation of Stat3 by autophagy in breast cancer cells have been previously reported and this can be mediated by IL-6 secretion that is controlled by autophagy related proteins (18).…”

Effect of the LncRNA GAS5-MiR-23a-ATG3 Axis in Regulating Autophagy in Patients with Breast Cancer

“…A previous study demonstrated that autophagy regulation has different and even opposite effects in breast cancer, indicating the need for a selection strategy when aiming to modulate autophagy in cancer therapy [30] . Interestingly, lncRNAs are reported to be critical regulators involved in tumour-related apoptosis, autophagy, and metastasis [31] .…”

Rna Sequencing and Pathway Analysis Identify Tumor Necrosis Factor Alpha Driven Small Proline-Rich Protein Dysregulation in Chronic Rhinosinusitis

“…After RNA-seq, derived sequences were analyzed by applying a custom computational pipeline that consisted of the opensource gSNAP, Cufflinks, and R for sequence alignment and ascertainment of differential gene expression. [12][13][14][15] In short, the reads generated were mapped to the human genome (hg10) by gSNAP, expression (fragments per kilobase of transcript per million mapped reads; FPKM) derived by Cufflinks, and differential expression was analyzed with analysis of variance in R. 16,17 Analyses of variance were performed to compare the expression levels of all four control subjects and all four subjects with CRS on a gene-by-gene basis. Once the gene list was formed, data were analyzed by using Ingenuity Pathway Analysis (Qiagen, Redwood City, CA).…”