Caveolin-1 inhibits breast cancer stem cells via c-Myc-mediated metabolic reprogramming

Wang, Shengqi; Wang, Neng; Zheng, Yifeng; Yang, Bowen; Liu, Pengxi; Zhang, Fengxue; Li, Min; Song, Ju‐Xian; Xu, Chang; Wang, Zhiyu

doi:10.1038/s41419-020-2667-x

Cited by 49 publications

(62 citation statements)

References 48 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In the present study, we further demonstrated that Cav-1 might act as the main pharmaceutical target of SA in suppressing metastasis on triple-negative breast cancer cell lines. This finding was also consistent with our previous study demonstrating that Cav-1 had higher expression in triple-negative breast cancer cell line MDA-MB-231 compared to other subtype cell lines ( Wang et al, 2020 ). Our pilot study also demonstrated that Cav-1 acts as the upstream regulator of NF-κB in breast cancer ( Jiao et al, 2019 ).…”

Section: Discussionsupporting

confidence: 93%

Sanguisorba officinalis L. Suppresses Triple-Negative Breast Cancer Metastasis by Inhibiting Late-Phase Autophagy via Hif-1α/Caveolin-1 Signaling

et al. 2020

Self Cite

View full text Add to dashboard Cite

Sanguisorba officinalis L. (SA) is a common herb for cancer treatment in the clinic, particularly during the consolidation phase to prevent occurrence or metastasis. Nevertheless, there are limited studies reporting the molecular mechanisms about its anti-metastatic function. It is well demonstrated that autophagy is one of the critical mechanisms accounting for metastasis and anti-cancer pharmacological actions of Chinese herbs. On the threshold, the regulatory effects and molecular mechanisms of SA in suppressing autophagy-related breast cancer metastasis were investigated in this study. In vitro findings demonstrated that SA potently suppressed the proliferation, colony formations well as metastasis process in triple-negative breast cancer. Network and biological analyses predicted that SA mainly targeted caveolin-1 (Cav-1) to induce anti-metastatic effects, and one of the core mechanisms was via regulation of autophagy. Further experiments—including western blotting, transmission electron microscopy, GFP-mRFP-LC3 immunofluorescence, and lysosomal-activity detection—validated SA as a potent late-stage autophagic inhibitor by increasing microtubule-associated light chain 3-II (LC3-II) conversion, decreasing acidic vesicular-organelle formation, and inducing lysosomal dysfunction even under conditions of either starvation or hypoxia. Furthermore, the anti-autophagic and anti-metastatic activity of SA was Cav-1-dependent. Specifically, Cav-1 knockdown significantly facilitated SA-mediated inhibition of autophagy and metastasis. Furthermore, hypoxia inducible factor-1α (Hif-1α) overexpression attenuated the SA-induced inhibitory activities on Cav-1, autophagy, and metastasis, indicating that SA may have inhibited autophagy-related metastasis via Hif-1α/Cav-1 signaling. In both mouse breast cancer xenograft and zebrafish xenotransplantation models, SA inhibited breast cancer growth and inhibited late-phase autophagy in vivo, which was accompanied by suppression of Hif-1α/Cav-1 signaling and the epithelial-mesenchymal transition. Overall, our findings not only indicate that SA acts as a novel late-phase autophagic inhibitor with anti-metastatic activities in triple-negative breast cancer, but also highlight Cav-1 as a regulator in controlling late-phase autophagic activity.

show abstract

Section: Discussionsupporting

confidence: 93%

Sanguisorba officinalis L. Suppresses Triple-Negative Breast Cancer Metastasis by Inhibiting Late-Phase Autophagy via Hif-1α/Caveolin-1 Signaling

et al. 2020

Self Cite

View full text Add to dashboard Cite

show abstract

“…E3 ligase SKP2, HUWE1, FBX29, TRUSS, RCHY1, CHIP, FBXW7, VHL, SPOP, TRIM32, NEDD4 and FBXL14 can target c-Myc for ubiquitination and degradation [149][150][151][152][153][154][155][156][157][158][159][160]. Decreased ubiquitination of c-Myc by VHL is observed to drive aerobic glycolysis in breast cancer cells [159]. Mutation or deletion of these E3 ligase genes induces carcinogenesis by attenuating c-Myc degradation.…”

Section: Ubiquitination Of C-mycmentioning

confidence: 99%

The role of ubiquitination and deubiquitination in cancer metabolism

Sun¹,

Liu²,

Yang³

2020

Mol Cancer

281

178

View full text Add to dashboard Cite

Metabolic reprogramming, including enhanced biosynthesis of macromolecules, altered energy metabolism, and maintenance of redox homeostasis, is considered a hallmark of cancer, sustaining cancer cell growth. Multiple signaling pathways, transcription factors and metabolic enzymes participate in the modulation of cancer metabolism and thus, metabolic reprogramming is a highly complex process. Recent studies have observed that ubiquitination and deubiquitination are involved in the regulation of metabolic reprogramming in cancer cells. As one of the most important type of post-translational modifications, ubiquitination is a multistep enzymatic process, involved in diverse cellular biological activities. Dysregulation of ubiquitination and deubiquitination contributes to various disease, including cancer. Here, we discuss the role of ubiquitination and deubiquitination in the regulation of cancer metabolism, which is aimed at highlighting the importance of this post-translational modification in metabolic reprogramming and supporting the development of new therapeutic approaches for cancer treatment.

show abstract

“…For example, cancer cells usually exhibit a metabolism switch characterized by decreased mitochondrial oxidative phosphorylation as well as elevated glycolysis, leading to the overproduction of toxic glucose metabolites. 161 The toxic glucose metabolites such as lactate, sorbitol, diacylglycerol (DAG), and methylglyoxal (MG) could further contribute to the development of advanced glycation end products (AGEs). On one hand, the formation of AGEs could impair the phagocytosis function of M1-like macrophages within the TME.…”

Section: Metabolic Signalingmentioning

confidence: 99%