USP5 Promotes Metastasis in Non-Small Cell Lung Cancer by Inducing Epithelial-Mesenchymal Transition via Wnt/β-Catenin Pathway

Xue, Sheliang; Wu, Wei; Wang, Ziyan; Lu, Guangxian; Sun, Jiantong; Jin, Xing; Xie, Linjun; Wang, Xiaoyu; Tan, Chunyan; Wang, Zheng; Wang, Wenjuan; Ding, Xinyuan

doi:10.3389/fphar.2020.00668

Cited by 30 publications

(26 citation statements)

References 33 publications

(36 reference statements)

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“…It is well known that dysregulated proliferation and metastasis are hallmarks of cancer cells (33,34), which is accountable for malignant features and poor prognosis of cancer patients. USP5 has been found to promote the epithelial-mesenchymal transition (EMT) and metastasis in NSCLC cells (35). Our cell model data together with Xue's data (35) have clarified that USP5 promotes the proliferation and metastatic malignant biological behaviors of NSCLC cells, thus providing a plausible explanation for the contribution of high level of USP5 to poor prognosis of NSCLC.…”

Section: Discussionmentioning

confidence: 51%

“…Nonetheless, our data showed that genetic manipulation of USP5 alone could modulate the CCND1 protein level in NSCLC cells in which USP22 was highly expressed, indicating that two members of the USP family, USP5 and USP22, can exert an additional effect in the stabilization of CCND1 via similar or distinct mechanisms. Previous studies have also found that upregulating USP5 facilitates the proliferation, EMT, and metastasis of NSCLC cells through the stabilization of β-catenin (23) and the activation of β-catenin signaling (23,35). It is well known that the transcription of CCND1, a classic downstream target of β-catenin, can be induced by the Wnt-β-catenin signaling pathway (46,47).…”

Section: Discussionmentioning

confidence: 98%

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Deubiquitinase USP5 promotes non-small cell lung cancer cell proliferation by stabilizing cyclin D1

Zhang¹,

Cui²,

Xie³

et al. 2021

Transl Lung Cancer Res

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Section: Discussionmentioning

confidence: 51%

Section: Discussionmentioning

confidence: 98%

Deubiquitinase USP5 promotes non-small cell lung cancer cell proliferation by stabilizing cyclin D1

Zhang¹,

Cui²,

Xie³

et al. 2021

Transl Lung Cancer Res

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“…Active β-Catenin signaling depends on its nuclear translocation and is strongly linked with EMT processes and aerobic glycolysis in different cancers ( Cai et al, 2018 ; Fang et al, 2019 ; Zuo et al, 2020 ). In CRC, dysregulated β-Catenin signaling participates in the regulation of tumor invasion, metastasis formation and aerobic metabolism, and various mutations in crucial regulatory factors of the Wnt/β-Catenin pathway have already been widely noted in CRC ( Jiao et al, 2020 ; Wang et al, 2020 ; Xue et al, 2020 ; Zhang et al, 2020 ).…”

Section: Discussionmentioning

confidence: 99%

Follistatin-Like 3 Enhances Invasion and Metastasis via β-Catenin-Mediated EMT and Aerobic Glycolysis in Colorectal Cancer

Tian

Liu

et al. 2021

Front. Cell Dev. Biol.

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Previous studies reported that Follistatin-like 3 (FSTL3) is abundantly expressed in several solid tumors and participate in the regulation of cell metabolism. However, the clinico-pathological significance, biological role and molecular mechanism of FSTL3 in colorectal cancer (CRC) is still unclear. Here we report that the expression level of FSTL3 in colon cancer specimens was significantly higher, compared to normal tissue and interestingly, the expression of FSTL3 was related to lymph node metastasis, tumor stage, tumor size, and intravascular emboli (IVE). As an upstream molecular event, we found that transcriptional regulation of FSTL3 was highly dependent on YAP1 de-phosphorylation events and that increased FSTL3 expression readily activated the β-Catenin pathway, which is a well-known signaling hub that promotes EMT processes and aerobic glycolysis in cancer cells. We found that elevated FSTL3 expression strongly promotes migration, invasion and metastatic formation of CRC cells by directly activating β-Catenin -mediated EMT and aerobic glycolysis. In the xenograft mouse model, FSTL3 expression was linked to increased metastatic formation of CRC cells. Together, the activation of YAP1 induces FSTL3 expression. FSTL3-mediated β-Catenin pathway activation promotes EMT and aerobic glycolysis and therefore affecting the invasive and metastatic capacity of CRC cells. The abundant FSTL3 expression is a poor prognostic factor and pharmacological targeting of YAP1 can counteract FSTL3 expression, suggesting a promising therapeutic target for anti-metastatic strategies in patients suffering from CRC.

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“…USP5, also named as isopeptidase T (IsoT), belongs to peptidase C19 family and prefer to cleave unanchored polyubiquitin chains [ 27 ], thus, it is crucial for free ubiquitin recycling. Besides its ubiquitin recycling function, USP5 is able to remove polyubiquitin chain on protein substrates and several proteins has been identified as USP5 substrates including FoxM1, c-Maf, and β-catenin [ 28 – 31 ]. It has been reported that knockdown of USP5 resulted in accumulation of unanchored polyubiquitin and activation of p53 pathway [ 32 ].…”

Section: Discussionmentioning

confidence: 99%

USP5 facilitates non-small cell lung cancer progression through stabilization of PD-L1

et al. 2021

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PD-L1(CD274) is a well-known immunosuppressive molecule, which confers immunoescape features to cancer cells and has become one of the major targets in cancer immunotherapies. Understanding the regulatory mechanisms that control PD-L1 protein expression is important for guiding immune checkpoint blockade therapy. Here, we showed that ubiquitin specific peptidase 5 (USP5) was a novel PD-L1 deubiquitinase in non-small cell lung cancer (NSCLC) cells. USP5 directly interacted with PD-L1 and deubiquitinated PD-L1, therefore enhances PD-L1 protein stability. Meanwhile, USP5 protein levels were highly elevated and positively correlated to PD-L1 levels in NSCLC tissues, and were closely correlated with poor prognosis of these patients. In addition, knockdown of USP5 retarded tumor growth in the Lewis lung carcinoma mouse model. Thus, we identified that USP5 was a new regulator of PD-L1 and targeting USP5 is a promising strategy for cancer therapy.

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USP5 Promotes Metastasis in Non-Small Cell Lung Cancer by Inducing Epithelial-Mesenchymal Transition via Wnt/β-Catenin Pathway

Cited by 30 publications

References 33 publications

Deubiquitinase USP5 promotes non-small cell lung cancer cell proliferation by stabilizing cyclin D1

Deubiquitinase USP5 promotes non-small cell lung cancer cell proliferation by stabilizing cyclin D1

Follistatin-Like 3 Enhances Invasion and Metastasis via β-Catenin-Mediated EMT and Aerobic Glycolysis in Colorectal Cancer

USP5 facilitates non-small cell lung cancer progression through stabilization of PD-L1

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