Tight junction protein 1 promotes vasculature remodeling via regulating USP2/TWIST1 in bladder cancer

Liu, Xue-Qi; Shao, Xin-Rong; Liu, Ye; Dong, Zhaoxia; Chan, Sze-Hoi; Shi, Yuanyuan; Chen, Shu-Na; Qi, Lin; Zhong, Li; Yu, Yue; Lv, Ting; Yang, Pengfei; Li, Liyan; Wang, Xiaobin; Zhang, Xudong; Li, Xin; Zhao, Wenxue; Sehgal, Lalit; Li, Miao; Zhang, Xingding

doi:10.1038/s41388-021-02112-w

Cited by 14 publications

(13 citation statements)

References 49 publications

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“…Moreover, the RNA sequencing analysis revealed that OCLN‐silenced cells exhibited downregulation of proangiogenic factors and IL8 (Figure 3B–E), further supporting the hypothesis that OCLN mediates tumorigenesis by regulating the expression and secretion of angiogenic factors. Another tight junction protein, TJP1, was also reported to promote vasculature remodelling in bladder cancer 30 . Although this report is the first to correlate OCLN and IL8 expression in BLCA angiogenesis, independent studies have revealed an association between IL8 and abnormal neovascularization properties.…”

Section: Discussionmentioning

confidence: 67%

“…BLCA cell lines, namely T24 (ATCC HTB‐4), 5637 (ATCC HTB‐9) were derived from laboratory retained cells 30 . Human umbilical vein endothelial cells (EA.hy926) (ATCC CRL‐2922) were purchased from Conservation Genetics CAS Kunming Cell Bank and 293T (ATCC CRL‐11268) cells were obtained from ATCC.…”

Section: Methodsmentioning

confidence: 99%

“…BLCA cell lines, namely T24 (ATCC HTB-4), 5637 (ATCC HTB-9) were derived from laboratory retained cells. 30 Human umbilical vein endothelial cells (EA.hy926) (ATCC CRL-2922) were purchased from Conservation Genetics CAS Kunming Cell Bank and 293T (ATCC CRL-11268) cells were obtained from ATCC. BLCA cell lines T24 and 5637 were cultured in RPMI-1640 medium (Gibco, Carlsbad, CA, USA) containing 10% foetal bovine serum (FBS) (AusgeneX, Brisbane, Queensland, Australia).…”

Section: Cell Culture and Reagentsmentioning

confidence: 99%

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Occludin facilitates tumour angiogenesis in bladder cancer by regulating IL8/STAT3 through STAT4

Yang

Liu

et al. 2022

J Cellular Molecular Medi

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Bladder cancer (BLCA) is a common genitourinary cancer in patients, and tumour angiogenesis is indispensable for its occurrence and development. However, the indepth mechanism of tumour angiogenesis in BLCA remains elusive. According to recent studies, the tight junction protein family member occludin (OCLN) is expressed at high levels in BLCA tissues and correlates with a poor prognosis. Downregulation of OCLN inhibits tumour angiogenesis in BLCA cells and murine xenografts, whereas OCLN overexpression exerts the opposite effect. Mechanistically, the RT-qPCR analysis and Western blotting results showed that OCLN increased interleukin-8 (IL8) and p-signal transducer and activator of transcription 3 (STAT3) levels to promote BLCA angiogenesis. RNA sequencing analysis and dual-luciferase reporter assays indicated that OCLN regulated IL8 transcriptional activity via the transcription factor STAT4. In summary, our results provide new perspectives on OCLN, as this protein participates in the development of BLCA angiogenesis by activating the IL8/STAT3 pathway via STAT4 and may serve as a novel and unique therapeutic target.

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Section: Discussionmentioning

confidence: 67%

Section: Methodsmentioning

confidence: 99%

Section: Cell Culture and Reagentsmentioning

confidence: 99%

See 1 more Smart Citation

Occludin facilitates tumour angiogenesis in bladder cancer by regulating IL8/STAT3 through STAT4

Yang

Liu

et al. 2022

J Cellular Molecular Medi

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“…Because a lack of neut B cells led to increased BBB permeability which is often detrimental to the host if not controlled, it was hypothesized that neut B cells play a necessary role in vascular repair attempts and vascular remodeling. To test this, infected control and neutrophil-depleted brains were incubated in antibodies for mature blood vessels (PECAM1+) and newly formed vessels (TJP1+) [23, 24], and ratios of newly formed blood vessels: total blood vessels were compared. Qualitative differences in staining for TJP1 were observed between blood vessels from infected control and neutrophil-depleted brains ( Fig.…”

Section: Resultsmentioning

confidence: 99%

Neutrophils in the brain are sources of neuroprotective molecules and demonstrate functional heterogeneity during chronicToxoplasma gondiiinfection

Bergersen

Kavvathas

David

et al. 2022

Preprint

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Infection with the protozoan parasite Toxoplasma gondii leads to the formation of lifelong cysts in neurons of the brain that can have devastating consequences in the immunocompromised. However, despite the establishment of a chronic inflammatory state and infection-induced neurological changes, there are limited signs of clinical neuropathology resulting in an asymptomatic infection in the immunocompetent. This suggests the work of neuroprotective mechanisms to prevent clinical manifestations of disease. However, such sources of neuroprotection during infection remain largely unknown. This study identifies a population of neutrophils chronically present in the brain during Toxoplasma infection that express the neuroprotective molecules NRG-1, ErbB4, and MSR1. Further phenotyping of this population via flow cytometry and singe-cell RNA sequencing reveals two distinct subsets of neutrophils based on age that display functional heterogeneity. This includes cells transcriptionally prepared to function both as anti-parasitic effector cells and in a more alternative protective manner. Chronic depletion of neutrophils results in increased parasite burden and infection-induced vascular pathology. Lack of neutrophils during chronic infection also deleteriously affects neuronal regeneration and repair mechanisms. In conclusion, this work identifies and demonstrates a functionally diverse chronic neutrophil population that plays a dynamic role in controlling infection outcome in the CNS by balancing classical responses with neuroprotective functions.

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“…USP2 inhibits ubiquitination and stabilizes cyclin A1, an important cell cycle regulator, raising the possibility of USP2 targeting as a combination of chemotherapy for bladder tumors [27]. In bladder cancer, Liu et al also discovered that tight junction protein 1 (TJP1) regulates TWIST1 expression by recruiting USP2, thereby regulating CCL2 expression and regulating angiogenesis in bladder cancer [46].…”

Section: Usp2 Acts As An Oncoprotein In Bladder Cancermentioning

confidence: 99%

Ubiquitin Specific Protease 2: Structure% Isoforms% Cellular Function% Related Diseases and Its Inhibitors

Luo¹,

Ji²,

Gao³

et al. 2022

Oncologie

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The ubiquitin-proteasome system (UPS) is an important pathway for cellular protein degradation. The components of this pathway, including the proteasome, ubiquitinase, and deubiquitinase, are highly specialized and strictly regulated. The ubiquitin-specific protease 2 (USP2) belongs to the ubiquitin-specific proteases, a subgroup of deubiquitinating enzymes. USP2 plays essential roles in regulating cell survival, cell cycle, circadian rhythm, cell metabolism, inflammatory response, antiviral response, and metastasis by interacting with certain proteins such as Cyclin D1, PER1, CRY1, HDM2/p53, FASN, LDLR, TRAF6, TBK1, and TGFBR1-TGFBR2 complex. Elevation of USP2 has been observed in a variety of cancers, including glioma, testicular cancer, breast cancer, prostate cancer, and some inflammatory diseases. Moreover, USP2 also plays an important role in many non-neoplastic diseases. At present, there is no officially approved USP2 inhibitor in clinic. A few existing inhibitors targeting USP2 have shown certain effects in the treatment of colorectal cancer, but their mechanism of action and binding site information are not clear. Moreover, the efficacy and selection specificity need to be further optimized. The catalytic centers of USP family are relatively conserved, so the design of compounds targeting allosteric site is expected to improve the specificity and inhibitory activity. In this review, we summarize the latest advances of USP2 in its cellular function, related diseases, and small-molecule inhibitors targeting USP2.

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Tight junction protein 1 promotes vasculature remodeling via regulating USP2/TWIST1 in bladder cancer

Cited by 14 publications

References 49 publications

Occludin facilitates tumour angiogenesis in bladder cancer by regulating IL8/STAT3 through STAT4

Occludin facilitates tumour angiogenesis in bladder cancer by regulating IL8/STAT3 through STAT4

Neutrophils in the brain are sources of neuroprotective molecules and demonstrate functional heterogeneity during chronicToxoplasma gondiiinfection

Ubiquitin Specific Protease 2: Structure% Isoforms% Cellular Function% Related Diseases and Its Inhibitors

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