USP37 Promotes Lung Cancer Cell Migration by Stabilizing Snail Protein via Deubiquitination

Cai, Jiali; Li, Mengying; Wang, Xiang; Li, Lei; Li, Qi; Hou, Zhaoyuan; Jia, Hong-Ti; Liu, Shiyuan

doi:10.3389/fgene.2019.01324

Cited by 40 publications

(34 citation statements)

References 43 publications

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“…By in vivo assay, USP37 downregulation also suppressed the tumor growth of MCF-7/ADR cells. The results are consistent with the previous reports that USP37 knockdown significantly inhibited the tumor formation of malignancies, such as lung cancer 18 , kidney cancer 19 , hepatocellular cancer 20 . Inordinate cell cycle progression resulted in tumorigenesis 21 .…”

Section: Discussionsupporting

confidence: 93%

USP37 downregulation elevates the Chemical Sensitivity of Human Breast Cancer Cells to Adriamycin

Qin¹,

Cui²,

Xiu³

et al. 2021

Int. J. Med. Sci.

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Background: The evolution of adriamycin (ADR) resistance in the treatment of breast cancer often leads to a poor prognosis in patients. Ubiquitin-specific peptidase 37 (USP37) has been recently identified as a modulator in regulating the stemness of breast cancer cells, but its underlying mechanism remains unclear. In this study, we investigated whether USP37 knockdown could hamper the chemical resistance of MCF-7 and MCF-7/ADR cells to adriamycin and elucidated the potential mechanism. Methods: Immunohistochemistry, western blotting, and RT-qPCR assays were performed to detect the USP37 expression in MCF-7 and MCF-7/ADR cells. The efficiency of USP37 knockdown in breast cancer cells was confirmed by western blotting and RT-qPCR assays. We also performed CCK-8 assay, flow cytometry, western blotting, and TUNEL assays to evaluate cell viability and apoptosis in breast cancer cells. In vivo study was performed to detect the tumorigenicity of MCF-7/ADR cells transfected with shScramble or shUSP37#1 under adriamycin treatment. Results: Bioinformatic analysis indicated that USP37 overexpression was positively correlated with adriamycin resistance. The expression levels of USP37 in both MCF-7 and MCF-7/ADR cells increased significantly with the exposure to adriamycin in a dose-dependent manner. It was verified by the observation that USP37 downregulation elevated the inhibitory effects of adriamycin on breast cancer cells, suppressed cell proliferation caused by cell cycle arrest in G1/S transition, as well as induced apoptosis. Furthermore, in vivo study showed that knockdown of USP37 expression also decreased tumorigenicity of MCF-7/ADR cells in mice. TUNEL assay and observation of cell morphology magnified USP37 knockdown synergized with Adriamycin could elevate the apoptosis of MCF-7 and MCF-7/ADR cells. Western blotting assay illustrated that the combination of USP37 knockdown with adriamycin treatment significantly upregulated the expression levels of cleaved caspase 3 and Bax, whereas the expression level of Bcl-2 was inhibited. Conclusion: Knockdown of USP37 gene expression can reverse the resistance of breast cancer cells to adriamycin, and down-regulating USP37 might be a valuable strategy against ADR resistance in breast cancer therapy.

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Section: Discussionsupporting

confidence: 93%

USP37 downregulation elevates the Chemical Sensitivity of Human Breast Cancer Cells to Adriamycin

Qin¹,

Cui²,

Xiu³

et al. 2021

Int. J. Med. Sci.

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“…It has been reported that expression of these factors is tightly controlled by DUBs. Snail protein can be deubiquitinated and stabilized by USP26, USP11, USP10, USP37 or OTUB1 [55][56][57][58][59]. Slug can be stabilized by USP10 and DUB3 [55,60].…”

Section: Discussionmentioning

confidence: 99%

The Deubiquitinase USP4 Stabilizes Twist1 Protein to Promote Lung Cancer Cell Stemness

et al. 2020

Cancers

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Lung cancer stem cells (CSCs) play a pivotal role in tumor development, drug resistance, metastasis and recurrence of lung cancer. Thus, it is of great importance to study the mechanism by which CSCs are regulated. In this study, we demonstrate that the deubiquitinase USP4 is critically important in promoting lung cancer stemness. Silencing of USP4 leads to reduction of Oct4 and Sox2 expression, decreased CD133+ cell population and inhibition of tumorsphere formation. Conversely, ectopic expression of USP4 significantly enhances lung cancer cell stemness, which is effectively rescued by simultaneous silencing of Twist1. Mechanistically, we identified USP4 as a novel deubiquitinase of Twist1. USP4 binds to, deubiquitinates and stabilizes Twist1 protein. Furthermore, we show that USP4 expression is elevated in human lung cancer specimens and is positively correlated with Twist1 expression. High expression of USP4/Twist1 is associated with poor clinical outcomes of lung cancer patients. Together, this study highlights an important role for USP4 in lung cancer stemness and suggests USP4 as a potential target for lung cancer diagnosis and treatment.

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“…Publicly available ChIP-seq datasets reveal JUN-1 and DAF-16 binding peaks upstream of math-33 (WormBase, release WS274), indicating direct transcriptional control by KGB-1-associated transcription factors. Dysregulation of deubiquitinases has been linked to several human diseases including cancers and neuropathologies 81 , 86 , 87 . Due to its association with KGB-1 and VHP-1, we implicate an additional role for MATH-33.…”

Section: Discussionmentioning

confidence: 99%

Trauma-induced regulation of VHP-1 modulates the cellular response to mechanical stress

et al. 2021

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Mechanical stimuli initiate adaptive signal transduction pathways, yet exceeding the cellular capacity to withstand physical stress results in death. The molecular mechanisms underlying trauma-induced degeneration remain unclear. In the nematode C. elegans, we have developed a method to study cellular degeneration in response to mechanical stress caused by blunt force trauma. Herein, we report that physical injury activates the c-Jun kinase, KGB-1, which modulates response elements through the AP-1 transcriptional complex. Among these, we have identified a dual-specificity MAPK phosphatase, VHP-1, as a stress-inducible modulator of neurodegeneration. VHP-1 regulates the transcriptional response to mechanical stress and is itself attenuated by KGB-1-mediated inactivation of a deubiquitinase, MATH-33, and proteasomal degradation. Together, we describe an uncharacterized stress response pathway in C. elegans and identify transcriptional and post-translational components comprising a feedback loop on Jun kinase and phosphatase activity.

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USP37 Promotes Lung Cancer Cell Migration by Stabilizing Snail Protein via Deubiquitination

Cited by 40 publications

References 43 publications

USP37 downregulation elevates the Chemical Sensitivity of Human Breast Cancer Cells to Adriamycin

USP37 downregulation elevates the Chemical Sensitivity of Human Breast Cancer Cells to Adriamycin

The Deubiquitinase USP4 Stabilizes Twist1 Protein to Promote Lung Cancer Cell Stemness

Trauma-induced regulation of VHP-1 modulates the cellular response to mechanical stress

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