WFDC2 suppresses prostate cancer metastasis by modulating EGFR signaling inactivation

Xiong, Yaoyi; Yuan, Lushun; Chen, Song; Xu, Huimin; Peng, Tianchen; Ju, Lingao; Wang, Gang; Xiao, Yu; Wang, Xinghuan

doi:10.1038/s41419-020-02752-y

Cited by 31 publications

(22 citation statements)

References 35 publications

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“…EMT is regulated by various signaling mechanisms, including cell surface receptor tyrosine kinases, and the associated interactions are important for its induction [ 22 , 23 ]. Epidermal growth factor receptor (EGFR) is one of the tyrosine kinases related to EMT [ 24 ].…”

Section: Resultsmentioning

confidence: 99%

Fusobacterium nucleatum Accelerates the Progression of Colitis-Associated Colorectal Cancer by Promoting EMT

Kim

Park

2020

Cancers

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Recently, it has been reported that Fusobacterium nucleatum, a major pathogen involved in chronic periodontitis, may play an important role in colorectal cancer (CRC) progression. In addition, inflammatory bowel diseases such as ulcerative colitis and Crohn’s disease represent major predisposing conditions for the development of CRC, and this subtype of cancer is called colitis-associated cancer (CAC). Although the importance of F. nucleatum in CRC has attracted attention, its exact role and related mechanism in CAC progression remain unclear. In this study, we investigated the effects of F. nucleatum in experimental colitis induced with dextran sodium sulfate (DSS), which is a well-known colitis-inducing chemical, on the aggressiveness of CAC and its related mechanism in both in vitro and in vivo models. F. nucleatum synergistically increased the aggressiveness and epithelial–mesenchymal transition (EMT) characteristics of CRC cells that were treated with DSS compared to those in non-treated CRC cells. The role of F. nucleatum in CAC progression was further confirmed in mouse models, as F. nucleatum was found to significantly increase the malignancy of azoxymethane (AOM)/DSS-induced colon cancer. This promoting effect of F. nucleatum was based on activation of the EGFR signaling pathways, including protein kinase B (AKT) and extracellular signal-regulated kinase (ERK), and epidermal growth factor receptor (EGFR) inhibition significantly reduced the F. nucleatum-induced EMT alteration. In conclusion, F. nucleatum accelerates the progression of CAC by promoting EMT through the EGFR signaling pathway.

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Section: Resultsmentioning

confidence: 99%

Fusobacterium nucleatum Accelerates the Progression of Colitis-Associated Colorectal Cancer by Promoting EMT

Kim

Park

2020

Cancers

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“… 21 WAP four-disulfide core domain 2 (WFDC2) inhibited the prostate cancer metastasis by suppressing EGFR signaling. 22 Spautin-1 treated the prostate cancer by the inhibition of EGFR signaling. 23 E-cad is a member of the cadherin family and widely exists in various epithelial cells.…”

Section: Discussionmentioning

confidence: 99%

<p>Regulating <em>DSC2</em> Expression Affects the Proliferation and Apoptosis of Prostate Cancer Cells</p>

Jiang¹,

Wu²

2020

CMAR

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Background: Prostate cancer threatens the life and health of men in China. Desmocollin-2 (DSC2) is a member of DSC family, abnormal expression of which can affect the invasion and metastasis of tumor cells. The aim of this study was to investigate the role of DSC2 in prostate cancer. Materials and Methods: Regulating DSC2 expression in prostate cancer cells was conducted with transfection. The expression of DSC2, apoptosis-related proteins, cell cyclerelated proteins and E-cadherin (E-cad)/β-catenin pathway was detected by Western blot analysis. The proliferation, clone formation ability, migration, invasion and apoptosis of transfected cells were in turn detected by cell counting kit-8 (CCK-8) assay, clone formation assay, wound healing assay, transwell assay and flow cytometry analysis. Results: DSC2 expression was increased in prostate cancer cells compared with RWPE-1 cells. Inhibition of DSC2 promoted the proliferation, clone formation ability, migration and invasion while suppressed apoptosis of LNCaP cells and PC-3 cells. Inhibition of DSC2 affected the expression of apoptosis-related proteins and cell cycle-related proteins according to the changes of apoptosis and proliferation. Furthermore, inhibition of DSC2 up-regulated the expression of p-βcatenin and EGFR while down-regulated the expression of E-cad. DSC2 overexpression exerted the opposite effect of inhibition of DSC2 on LNCaP cells and PC-3 cells. Conclusion: DSC2 expression was increased in prostate cancer cells. In addition, inhibition of DSC2 promoted the proliferation, clone formation ability, migration and invasion while suppressed apoptosis of LNCaP cells and PC-3 cells, which provided the fundamental basis for treatment of prostate cancer.

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“…Then, the cells were treated by an ultrasonic crusher for 10 s and centrifuged at 14,000 × g for 10 min. Protein separation and detection were performed as previously described 58 . Finally, immune response bands were exposed in the electromagnetic interference XRS imaging system (Bio-Rad, USA).…”

Section: Methodsmentioning

confidence: 99%

E3 ubiquitin ligase RNF126 affects bladder cancer progression through regulation of PTEN stability

Xiong

et al. 2021

Cell Death Dis

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E3 ubiquitin ligase RNF126 (ring finger protein 126) is highly expressed in various cancers and strongly associated with tumorigenesis. However, its specific function in bladder cancer (BCa) is still debatable. Here, we found that RNF126 was significantly upregulated in BCa tissue by TCGA database, and our studies indicated that downregulation of RNF126 significantly inhibited cell proliferation and metastasis through the EGFR/PI3K/AKT signaling pathway in BCa cells. Furthermore, we identified PTEN, an inhibitor of the PI3K/AKT signaling pathway, as a novel substrate for RNF126. By co-immunoprecipitation assays, we proved that RNF126 directly interacts with PTEN. Predominantly, PTEN binds to the C-terminal containing the RING domain of RNF126. The in vivo ubiquitination assay showed that RNF126 specifically regulates PTEN stability through poly-ubiquitination. Furthermore, PTEN knockdown restored cell proliferation, metastasis, and tumor formation of BCa cells inhibited by RNF126 silencing in vitro and in vivo. In conclusion, these results identified RNF126 as an oncogene that functions through ubiquitination and degradation of PTEN in BCa.

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WFDC2 suppresses prostate cancer metastasis by modulating EGFR signaling inactivation

Cited by 31 publications

References 35 publications

Fusobacterium nucleatum Accelerates the Progression of Colitis-Associated Colorectal Cancer by Promoting EMT

Fusobacterium nucleatum Accelerates the Progression of Colitis-Associated Colorectal Cancer by Promoting EMT

<p>Regulating <em>DSC2</em> Expression Affects the Proliferation and Apoptosis of Prostate Cancer Cells</p>

E3 ubiquitin ligase RNF126 affects bladder cancer progression through regulation of PTEN stability

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