Autophagy maintains the stemness of ovarian cancer stem cells by FOXA2.

J Exp Clin Cancer Res

Department of Gynecologic Oncology; Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, 310006, China.

Published: November 2017

Background: Cancer stem cells (CSCs) are regarded as the main cell type responsible for the initiation, metastasis, drug resistance, and recurrence of cancer. But the mechanism by which cancer stem cells maintain their stemness remains unclear.

Methods And Results: In the present study, ovarian cancer stem cells (OCSCs) were revealed to have an enhanced autophagic flux. Furthermore, their chemoresistance and ability to self-renewal in vitro were decreased when autophagy was inhibited by Bafilomycin A1(BafA1), Chloroquine(CQ) or autophagy related 5(ATG5) knockdown. PCR array screening determined that Forkhead Box A2(FOXA2) was highly expressed in OCSCs, and correspondingly regulated by autophagy activity. In addition, the self-renewal ability was decreased in the case of FOXA2 knockdown by shRNA in OCSCs. Overexpression of FOXA2 from the pEGFP(+)-FOXA2 plasmid partially reversed the depressed self-renewal ability of OCSCs during autophagy inhibition.

Conclusions: Our findings suggest that autophagy, through participation of FOXA2, maintains the characteristics of OCSCs. Autophagy and FOXA2 are therefore potential targets for ovarian cancer stem cell directed therapies.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5707869PMC
http://dx.doi.org/10.1186/s13046-017-0644-8DOI Listing

Publication Analysis

Top Keywords

cancer stem
20
stem cells
16
ovarian cancer
12
self-renewal ability
8
ocscs autophagy
8
autophagy
7
cancer
6
stem
5
foxa2
5
ocscs
5

Similar Publications

MTHFD2 promotes breast cancer cell proliferation through IFRD1 RNA m6A methylation-mediated HDAC3/p53/mTOR pathway.

Neoplasma

December 2024

Department of Pathology and Forensic Medicine, College of Basic Medical Sciences, Dalian Medical University, Dalian, China.

MTHFD2 is highly overexpressed in breast cancer tissues, indicating that it might be used as a target in breast cancer treatment. This study aims to determine the role of MTHFD2 in breast cancer cell proliferation and the molecular pathways involved. In order to investigate MTHFD2 gene expression and its downstream pathways in breast cancer, we started our inquiry with a bioinformatics analysis.

View Article and Find Full Text PDF

Pediatric central nervous system (CNS) tumors represent 20-25% of childhood malignancies, with 35-40 new cases annually in Slovakia. Despite treatment advances, high mortality and poor quality of life in a lot of cases persist. This study assesses the clinical features, treatment modalities, and survival rates of pediatric CNS tumor patients in the single largest center in Slovakia.

View Article and Find Full Text PDF

Impact of calreticulin mutations on treatment and survival outcomes in myelofibrosis during ruxolitinib therapy.

Ann Hematol

January 2025

Department of Engineering for Innovation Medicine, Section of Innovation Biomedicine, Hematology Area, University of Verona, Verona, Italy.

Calreticulin (CALR) mutations are detected in around 20% of patients with primary and post-essential thrombocythemia myelofibrosis (MF). Regardless of driver mutations, patients with splenomegaly and symptoms are generally treated with JAK2-inhibitors, most commonly ruxolitinib. Recently, new therapies specifically targeting the CALR mutant clone have entered clinical investigation.

View Article and Find Full Text PDF

Extracellular vesicle-mediated VEGF-A mRNA delivery rescues ischaemic injury with low immunogenicity.

Eur Heart J

January 2025

School of Chemical Biology and Biotechnology, Peking University Shenzhen Graduate School, Shenzhen, 2199 Lishui Rd, Nanshan, Shenzhen, Guangdong Province 518055, China.

Background And Aims: Lackluster results from recently completed gene therapy clinical trials of VEGF-A delivered by viral vectors have heightened the need to develop alternative delivery strategies. This study aims to demonstrate the pre-clinical efficacy and safety of extracellular vesicles (EVs) loaded with VEGF-A mRNA for the treatment of ischaemic vascular disease.

Methods: After encapsulation of full-length VEGF-A mRNA into fibroblast-derived EVs via cellular nanoporation (CNP), collected VEGF-A EVs were delivered into mouse models of ischaemic injury.

View Article and Find Full Text PDF

Hypoxia is a common phenomenon for solid tumors due to a lack of effective vascular system, and has been deemed as an important factor that drives the progression of thyroid cancer (TC) via altering the characteristics of tumor cells. The present study suggested that hypoxic TC cells enhanced cancer stem cell properties and progression of TC by delivering long intergenic non-protein coding RNA 665 (LINC00665)-containing exosomes. Specifically, TPC1 cells were exposed to normoxic or hypoxic environment, and it was found that hypoxic TPC1 cells-secreted exosomes (H-exo) were enriched with LINC00665, compared to normoxic TPC1 cells-derived exosomes (N-exo).

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!