Forkhead Box Q1 is a novel regulator of autophagy in breast cancer cells

Abstract

Forkhead Box Q1 (FoxQ1) transcription factor is overexpressed in luminal‐type and basal‐type human breast cancers when compared to normal mammary tissue. This transcription factor is best known for its role in promotion of breast cancer stem‐like cells and epithelial to mesenchymal transition. The present study documents a novel function of FoxQ1 in breast cancer cells. Overexpression of FoxQ1 in basal‐like SUM159 cells and luminal‐type MCF‐7 cells resulted in increased conversion of microtubule‐associated protein light chain 3 beta‐I (LC3B‐I) to LC3B‐II, which is a hallmark of autophagy. Autophagy induction by FoxQ1 overexpression was confirmed by visualization of LC3B puncta as well as by transmission electron microscopy. Expression profiling for genes implicated in autophagy regulation revealed upregulation of many genes, including ATG4B, ATG16L1, CTSS, CXCR4 and so forth but downregulation of BCL2L1, DRAM1, TNF, ULK2 and so forth by FoxQ1 overexpression in SUM159 cells. Western blot analysis confirmed upregulation of ATG4B and CXCR4 proteins by FoxQ1 overexpression in both SUM159 and MCF‐7 cells. Chromatin immunoprecipitation assay revealed recruitment of FoxQ1 at the promoter of ATG4B. Pharmacological inhibition of ATG4B using S130 significantly increased apoptosis induction by DOX in empty vector transfected as well as FoxQ1 overexpressing SUM159 and MCF‐7 cells but this effect was statistically significantly lowered by FoxQ1 overexpression indicating the protective role of FoxQ1 on apoptosis. Treatment of SUM159 cells with S130 and DOX enhanced LC3B‐II level in both empty vector transfected cells and FoxQ1 overexpressing SUM159 cells but not in FoxQ1 overexpressing MCF‐7 cells. In conclusion, FoxQ1 is a novel regulator of autophagy.

FOXQ1 inhibits the progression of osteoarthritis by regulating pyroptosis

“…OA is a typical age-related immune disease, and FOXQ1 is involved in the regulation of senescence-associated inflammation [19]. Moreover, FOXQ1 has been a potential prognostic and biomarker for a variety of cancers, such as colorectal cancer and breast cancer [20][21][22], but the research on orthopedic disease is extremely rare. In recent years, studies have found that FOXQ1 has the potential to promote the osteogenic differentiation of bone mesenchymal stem cells [23][24][25].…”