UCP1 regulates ALDH-positive breast cancer stem cells through releasing the suppression of Snail on FBP1

Zhang, Fuchuang; Liu, Bingjie; Deng, Qiaodan; Sheng, Dandan; Xu, Jiahui; He, Xueyan; Zhang, Lixing; Liu, Suling

doi:10.1007/s10565-020-09533-5

Cited by 14 publications

(11 citation statements)

References 42 publications

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“…GAPDH was used as an internal control to normalize the expression of other mRNAs. Relative gene expression was calculated using the 2 –ΔΔ Ct method ( Zhang F. et al, 2020 ).…”

Section: Methodsmentioning

confidence: 99%

RETRACTED: Abnormal Mitochondria-Endoplasmic Reticulum Communication Promotes Myocardial Infarction

Cheng

Zheng

et al. 2021

Front. Physiol.

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Myocardial infarction is characterized by cardiomyocyte death, and can be exacerbated by mitochondrial damage and endoplasmic reticulum injury. In the present study, we investigated whether communication between mitochondria and the endoplasmic reticulum contributes to cardiomyocyte death after myocardial infarction. Our data demonstrated that hypoxia treatment (mimicking myocardial infarction) promoted cardiomyocyte death by inducing the c-Jun N-terminal kinase (JNK) pathway. The activation of JNK under hypoxic conditions was dependent on overproduction of mitochondrial reactive oxygen species (mtROS) in cardiomyocytes, and mitochondrial division was identified as the upstream inducer of mtROS overproduction. Silencing mitochondrial division activators, such as B cell receptor associated protein 31 (BAP31) and mitochondrial fission 1 (Fis1), repressed mitochondrial division, thereby inhibiting mtROS overproduction and preventing JNK-induced cardiomyocyte death under hypoxic conditions. These data revealed that a novel death-inducing mechanism involving the BAP31/Fis1/mtROS/JNK axis promotes hypoxia-induced cardiomyocyte damage. Considering that BAP31 is localized within the endoplasmic reticulum and Fis1 is localized in mitochondria, abnormal mitochondria-endoplasmic reticulum communication may be a useful therapeutic target after myocardial infarction.

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“…GAPDH was used as an internal control to normalize the expression of other mRNAs. Relative gene expression was calculated using the 2 –ΔΔ Ct method ( Zhang F. et al, 2020 ).…”

Section: Methodsmentioning

confidence: 99%

RETRACTED: Abnormal Mitochondria-Endoplasmic Reticulum Communication Promotes Myocardial Infarction

Cheng

Zheng

et al. 2021

Front. Physiol.

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“…These include classical stem-cell pathways such as Wnt/β-catenin (beta), Notch, and Hh, which regulate cell fate and tissue patterning in early life, as well as cZEBell proliferation axes such as JAK/signal transducer and activator of transcription 3 (STAT3)/5 [11,[13][14][15]24] . Regulators of Epithelial-to-Mesenchymal Transition (EMT), an essential developmental process during organogenesis, including SNAIL, and twist family bHLH transcription factor 1 (TWIST) transcription factors, are also vital to TNBC stemness [25][26][27] . Recent evidence also suggests TME hypoxia and increased activity of pluripotency mediators such as OCT4, SOX2, and master regulator of cell cycle entry and proliferative metabolism (MYC), in TNBC compared to non-TNBC breast cancer, contribute to the elevated stemness phenotype [28][29][30] .…”

Section: Cellular Pathways Regulating Stemness In Tnbcmentioning

confidence: 99%

“…The SNAIL-induced glycolytic switch to a more "Warburg"-like state reduces oxygen consumption and reactive oxygen species (ROS) accumulation, promoting tumorigenesis, survival, and self-renewal [126] . Recent work by Zhang et al [25] suggests uncoupling Protein 1 (UCP1), which is downregulated in TNBC, represses SNAIL-mediated FBP1 silencing, suppressing TNBCSC accumulation. BRD4 also promotes SNAIL expression in TNBC, conferring TNBC cells with stem-cell-like traits [127] .…”

Section: Snailmentioning

confidence: 99%

Regulation of cancer stem cells in triple negative breast cancer

Fultang¹,

Chakraborty²,

Peethambaran³

2021

CDR

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Triple Negative Breast Cancer (TNBC) is the most lethal subtype of breast cancer. Despite the successes of emerging targeted therapies, relapse, recurrence, and therapy failure rates in TNBC significantly outpace other subtypes of breast cancer. Mounting evidence suggests accumulation of therapy resistant Cancer Stem Cell (CSC) populations within TNBCs contributes to poor clinical outcomes. These CSCs are enriched in TNBC compared to non-TNBC breast cancers. The mechanisms underlying CSC accumulation have been well-characterized and discussed in other reviews. In this review, we focus on TNBC-specific mechanisms that allow the expansion and activity of self-renewing CSCs. We highlight cellular signaling pathways and transcription factors, specifically enriched in TNBC over non-TNBC breast cancer, contributing to stemness. We also analyze publicly available singlecell RNA-seq data from basal breast cancer tumors to highlight the potential of emerging bioinformatic approaches in identifying novel drivers of stemness in TNBC and other cancers.

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“…Those inhibition effects were similar in the breast cancer cell line HCC1806 11 . In ALDH-positive breast cancer stem cells, UCP1 could reduce the inhibitory effect of Snail on glucose metabolism enzyme FBP1, suppressing the tumor progress 12 . Those researches showed a therapeutic potential of UCP1 on cancer through glucose and lipid metabolism regulation, whereas the mitochondrial regulation potential of UCP1 on breast cancer was insufficient.…”

Section: Introductionmentioning

confidence: 99%

Mitochondrial Protein UCP1 Inhibits the Malignant Behaviors of Triple-negative Breast Cancer through Activation of Mitophagy and Pyroptosis

Xia¹,

Chu²,

Li³

et al. 2022

Int. J. Biol. Sci.

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Triple-negative breast cancer (TNBC) is a massive threat to women's health due to its high morbidity, malignancy, and the refractory, effective therapeutic option of TNBC is still deficient. The mitochondrial protein showed therapeutic potential on breast cancer, whereas the mechanism and downstream pathway of mitochondrial uncoupling protein 1 (UCP1) was not fully elucidated. We found that UCP1 was negatively regulated to the process of TNBC. Overexpressing UCP1 could inhibit the proliferation and metastasis of TNBC, meanwhile inducing the mitochondrial swelling and activation of mitophagy in vitro . Mitophagy activation was then assessed to elucidate whether it was downstream of UCP1 in TNBC metastasis. GSDME is the core of pyroptosis. We found that GSDME was activated in the TNBC cells when UCP1 levels were high. It regulates TNBC cell proliferation potential instead of the apoptosis process in vitro and in vivo . Our results suggested that UCP1 could inhibit the process of TNBC by activating mitophagy and pyroptosis. Impaired activation of mitophagy weakens the regulation effect of UCP1 on metastasis of TNBC, similar to the impairment of GSDME activation on the proliferation regulation of UCP1 on TNBC. UCP1 might be a novel therapeutic target of TNBC.

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UCP1 regulates ALDH-positive breast cancer stem cells through releasing the suppression of Snail on FBP1

Cited by 14 publications

References 42 publications

RETRACTED: Abnormal Mitochondria-Endoplasmic Reticulum Communication Promotes Myocardial Infarction

RETRACTED: Abnormal Mitochondria-Endoplasmic Reticulum Communication Promotes Myocardial Infarction

Regulation of cancer stem cells in triple negative breast cancer

Mitochondrial Protein UCP1 Inhibits the Malignant Behaviors of Triple-negative Breast Cancer through Activation of Mitophagy and Pyroptosis

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