Breast cancer stem cells (CSCs) are difficult to therapeutically target, but continued efforts are critical given their contribution to tumor heterogeneity and treatment resistance in triple-negative breast cancer. CSC properties are influenced by metabolic stress, but specific mechanisms are lacking for effective drug intervention. Our previous work on TFEB suggested a key function in CSC metabolism. Indeed, TFEB knockdown (KD) inhibited mammosphere formation in vitro and tumor initiation/growth in vivo. These phenotypic effects were accompanied by a decline in CD44/CD24 cells. Glycolysis inhibitor 2-deoxy-D-glucose (2-DG) induced TFEB nuclear translocation, indicative of TFEB transcriptional activity. TFEB KD blunted, whereas TFEB (S142A) augmented 2-DG-driven unfolded protein response (UPR) mediators, notably BiP/HSPA5 and CHOP. Like TFEB KD, silencing BiP/HSPA5 inhibited CSC self-renewal, suggesting that TFEB augments UPR-related survival. Further studies showed that TFEB KD attenuated 2-DG-directed autophagy, suggesting a mechanism whereby TFEB protects CSCs against 2-DG-induced stress. Our data indicate that TFEB modulates CSC metabolic stress response via autophagy and UPR. These findings reveal the novel role of TFEB in regulating CSCs during metabolic stress in triple-negative breast cancer.

Download full-text PDF

Source
http://dx.doi.org/10.26508/lsa.202302259DOI Listing

Publication Analysis

Top Keywords

metabolic stress
16
tfeb
13
breast cancer
12
stem cells
8
triple-negative breast
8
stress
5
transcription factor
4
factor tfeb
4
tfeb activity
4
activity increases
4

Similar Publications

Background: Non-structural carbohydrates (NSCs) are key substances for metabolic processes in plants, providing energy for growth, development, and responses to environmental stress. Pruning mother bamboo in a clump can significantly affect the NSCs allocation of new shoots, thereby affecting their growth. Moso bamboo (Phyllostachys edulis) is an important economic bamboo species with a highest planting area in China.

View Article and Find Full Text PDF

Identification of EXPA4 as a key gene in cotton salt stress adaptation through transcriptomic and coexpression network analysis of root tip protoplasts.

BMC Plant Biol

January 2025

National Key Laboratory of Cotton Bio-breeding and Integrated Utilization, Institute of Cotton Research, Chinese Academy of Agricultural Sciences, Anyang, Henan, 455000, China.

Background: Salinity stress impairs cotton growth and fiber quality. Protoplasts enable elucidation of early salt-responsive signaling. Elucidating crop tolerance mechanisms that ameliorate these diverse salinity-induced stresses is key for improving agricultural productivity under saline conditions.

View Article and Find Full Text PDF

TaSnRK3.23B, a CBL-interacting protein kinase of wheat, confers drought stress tolerance by promoting ROS scavenging in Arabidopsis.

BMC Plant Biol

January 2025

Institute of Food Crops, Hubei Academy of Agricultural Sciences/Key Laboratory of Crop Molecular Breeding, Ministry of Agriculture and Rural Affairs/Hubei Key Laboratory of Food Crop Germplasm and Genetic Improvement, Wuhan, 430064, China.

Background: Sucrose non-fermenting-1-related protein kinases (SnRKs) have been implicated in plant growth and stress responses. Although SnRK3.23 is known to be involved in drought stress, the underlying mechanism of resistance differs between Arabidopsis and rice, and little is known about its function in wheat.

View Article and Find Full Text PDF

AUTS2 syndrome is characterized by intellectual disability and microcephaly, and is often associated with autism spectrum disorder, but the underlying mechanisms, particularly concerning microcephaly, remain incompletely understood. Here, we analyze mice mutated for the transcriptional regulator AUTS2, which recapitulate microcephaly. Their brains exhibit reduced division of intermediate progenitor cells (IPCs), leading to fewer neurons and decreased thickness in the upper-layer cortex.

View Article and Find Full Text PDF

Astragaloside IV attenuates cadmium induced nephrotoxicity in rats by activating Nrf2.

Sci Rep

January 2025

Department of Nephrology, the Key Laboratory for the Prevention and Treatment of Chronic Kidney Disease of Chongqing, Chongqing Clinical Research Center of Kidney and Urology Diseases, Xinqiao Hospital, Army Medical University, (Third Military Medical University), Chongqing, China.

Acute kidney injury (AKI) has become a disease of global concern due to its high morbidity and mortality. This has highlighted the need for renoprotective agents. Astragaloside IV (AS-IV) is a saponin isolated from Astragalus membranaceus with good antioxidant, anti-inflammatory and anti-tumor properties.

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!