MAPK1/3 kinase-dependent ULK1 degradation attenuates mitophagy and promotes breast cancer bone metastasis

Deng, Rong; Zhang, Hai-Liang; Huang, Junhao; Cai, Ruizhao; Wang, Yan; Chen, Yuhong; Hu, Bingxin; Ye, Zhipeng; Li, Zhiling; Mai, Jia; Huang, Yun; Li, Xuan; Peng, Xiaoxue; Gao, Feng; Li, Jun‐Dong; Tang, Jun; Zhu, Xiao‐Feng

doi:10.1080/15548627.2020.1850609

Cited by 118 publications

(80 citation statements)

References 60 publications

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“…Moreover, the protein level of ULK1 was upregulated and that of MAPKAP1 was downregulated in PAMR1-overexpressed HeLa cells, whereas opposite results were observed in PAMR1 knockdown cells ( Supplementary Figure S7A ). As an autophagy initiation factor, ULK1 has been proven to promote autophagic flux and inhibit cancer progress and metastasis ( 19 , 20 ). We then examined the effect of PAMR1 on autophagy using Western blot.…”

Section: Resultsmentioning

confidence: 99%

High Expression of PAMR1 Predicts Favorable Prognosis and Inhibits Proliferation, Invasion, and Migration in Cervical Cancer

Yang

et al. 2021

Front. Oncol.

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Peptidase domain containing associated with muscle regeneration 1 (PAMR1) is frequently lost in breast cancer samples and is considered as a tumor suppressor. The roles and mechanisms of PAMR1 in other types of cancers are still unclear. In our present study, we identified PAMR1 as an invasion-related regulator in cervical cancer. Public database and immunohistochemical (IHC) analysis showed that the expression level of PAMR1 in cervical cancer tissues was lower than that in normal cervix tissues and was negatively related to clinicopathologic features. The high expression of PAMR1 also predicted a better prognosis of cervical cancer patients. CCK8, Transwell, and wound-healing assays demonstrated that knockdown of PAMR1 facilitated the proliferation, migration, and invasion of cervical cancer cells. Additionally, gene set enrichment analysis (GSEA) showed a variety of cancer-related pathways potentially activated or suppressed by PAMR1. Moreover, we verified that PAMR1 inhibited MYC target and mTORC1 signaling pathways. In conclusion, our study revealed the suppressor role of PAMR1 in cervical cancer, providing a new insight into the molecular mechanism of cervical cancer progression.

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Section: Resultsmentioning

confidence: 99%

High Expression of PAMR1 Predicts Favorable Prognosis and Inhibits Proliferation, Invasion, and Migration in Cervical Cancer

Yang

et al. 2021

Front. Oncol.

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“…Sci. 2021, 22, 9283 2 of 12 growth and metastasis and predicted poor metastasis-free survival [3,4]. On the contrary, data showed activation of mitophagy reduced drug-induced apoptosis in breast cancer cells, suggesting that once a tumor has progressed to an advanced stage, mitophagy may mitigate the treatment-induced stress and participate in the chemoresistance of cancer cells [5,6].…”

Section: Introductionmentioning

confidence: 99%

Doxorubicin-Induced Autophagolysosome Formation Is Partly Prevented by Mitochondrial ROS Elimination in DOX-Resistant Breast Cancer Cells

Ahmadpour

Desquiret-Dumas

Yikilmaz

et al. 2021

IJMS

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Since its discovery, mitophagy has been viewed as a protective mechanism used by cancer cells to prevent the induction of mitochondrial apoptosis. Most cancer treatments directly or indirectly cause mitochondrial dysfunction in order to trigger signals for cell death. Elimination of these dysfunctional mitochondria by mitophagy could thus prevent the initiation of the apoptotic cascade. In breast cancer patients, resistance to doxorubicin (DOX), one of the most widely used cancer drugs, is an important cause of poor clinical outcomes. However, the role played by mitophagy in the context of DOX resistance in breast cancer cells is not well understood. We therefore tried to determine whether an increase in mitophagic flux was associated with the resistance of breast cancer cells to DOX. Our first objective was to explore whether DOX-resistant breast cancer cells were characterized by conditions that favor mitophagy induction. We next tried to determine whether mitophagic flux was increased in DOX-resistant cells in response to DOX treatment. For this purpose, the parental (MCF-7) and DOX-resistant (MCF-7dox) breast cancer cell lines were used. Our results show that mitochondrial reactive oxygen species (ROS) production and hypoxia-inducible factor-1 alpha (HIF-1 alpha) expression are higher in MCF-7dox in a basal condition compared to MCF-7, suggesting DOX-resistant breast cancer cells are prone to stimuli to induce a mitophagy-related event. Our results also showed that, in response to DOX, autophagolysosome formation is induced in DOX-resistant breast cancer cells. This mitophagic step following DOX treatment seems to be partly due to mitochondrial ROS production as autophagolysosome formation is moderately decreased by the mitochondrial antioxidant mitoTEMPO.

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“…Recent evidence reveals that MAPK1 signaling is involved in the regulation of cell differentiation (Deng et al, 2020). It has been shown that licochalcone A induces the osteogenic differentiation through activation of MAPK1 .…”

Section: Discussionmentioning

confidence: 99%

Decoding the Mechanism of Shen Qi Sha Bai Decoction in Treating Acute Myeloid Leukemia Based on Network Pharmacology and Molecular Docking

Jia¹,

Jiang²,

Li³

et al. 2021

Front. Cell Dev. Biol.

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Traditional Chinese Medicine (TCM) has been shown to be efficacious in treating leukemia for thousands of years. It has been shown that Shen Qi Sha Bai Decoction (SQSBD) has been extensively used in the treatment of acute myeloid leukemia (AML). However, the mechanism of SQSBD in treating AML remains unclear. In this study, we employed network pharmacology to analyze the potential active components and elucidate molecular mechanism of SQSBD in treating AML. A total of 268 active components were identified from SQSBD, among which 9 key components (Quercetin, luteolin, kaempferol, licochalcone A, formononetin, wogonin, β-sitosterol, oroxylin A, naringenin, and baicalein) were hit by the 6 hub targets (CDK1, MAPK1, JUN, PCNA, HSB1, STAT3) associated with leukemia. Molecular docking showed that two core active components, quercetin and licochalcone A, exhibited the highest component-like properties (DL), and could bind well to CDK1 and MAPK1 protein. The experimental validation of these two components showed that quercetin inhibited cell growth through CDK1 dephosphorylation-mediated cell cycle arrest at G2/M phase in human AML U937 and HL60 cells, and licochalcone A induced cell differentiation in these leukemia cells via activation of MAPK1 and upregulation of CD11b. All these results indicate that SQSBD is effective in the treatment of AML, and quercetin and licochalcone A are the major candidate compounds for AML treatment.

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MAPK1/3 kinase-dependent ULK1 degradation attenuates mitophagy and promotes breast cancer bone metastasis

Cited by 118 publications

References 60 publications

High Expression of PAMR1 Predicts Favorable Prognosis and Inhibits Proliferation, Invasion, and Migration in Cervical Cancer

High Expression of PAMR1 Predicts Favorable Prognosis and Inhibits Proliferation, Invasion, and Migration in Cervical Cancer

Doxorubicin-Induced Autophagolysosome Formation Is Partly Prevented by Mitochondrial ROS Elimination in DOX-Resistant Breast Cancer Cells

Decoding the Mechanism of Shen Qi Sha Bai Decoction in Treating Acute Myeloid Leukemia Based on Network Pharmacology and Molecular Docking

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