FAT10: Function and Relationship with Cancer

Xiang, Senfeng; Shao, Xuejing; Cao, Ji; Yang, Bo; He, Qiaojun

doi:10.2174/1874467212666191113130312

Cited by 17 publications

(10 citation statements)

References 73 publications

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“…This enzyme has been shown to influence many cellular processes, including cell cycle regulation [ 20 ]. In recent, the influence of FAT10 on the malignant tumours is investigated extensively [ 34 ], while other studies reported that the FAT10 is participated in renal disease pathogenesis [ 22 , 23 ]. However, there is currently no information on the impact of FAT10 on the renal fibrosis.…”

Section: Discussionmentioning

confidence: 99%

Ubiquitin-like protein FAT10 promotes renal fibrosis by stabilizing USP7 to prolong CHK1-mediated G2/M arrest in renal tubular epithelial cells

Shao

Zhang

et al. 2022

Aging

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Renal fibrosis is the pathological hallmark of chronic kidney disease that is influenced by numerous factors. Arrest of renal tubular epithelial cells (RTECs) in G2/M phase is closely correlated with the progression of renal fibrosis; however, the mechanisms mediating these responses remain poorly defined. In this study, we observed that human leukocyte antigen-F adjacent transcript 10 (FAT10) deficiency abolished hypoxia-induced upregulation of checkpoint kinase 1 (CHK1) expression in RTECs derived from FAT10 +/+ and FAT10 −/− mice. Further investigations revealed that FAT10 contributes to CHK1-mediated G2/M arrest and production of pro-fibrotic cytokines in RTECs exposed to hypoxia. Mechanistically, FAT10 directly interacted with and stabilized the deubiquitylating enzyme ubiquitin specific protease 7 (USP7) to mediate CHK1 upregulation, thereby promoting CHK1-mediated G2/M arrest in RTECs. In animal model, FAT10 expression was upregulated in the obstructed kidneys of mice induced by unilateral ureteric obstruction injury, and FAT10 −/− mice exhibited reduced unilateral ureteric obstruction injury induced-renal fibrosis compared with FAT10 +/+ mice. Furthermore, in a cohort of patients with calculi-related chronic kidney disease, upregulated FAT10 expression was positively correlated with renal fibrosis and the USP7/CHK1 axis. These novel findings indicate that FAT10 prolongs CHK1-mediated G2/M arrest via USP7 to promote renal fibrosis, and inhibition of the FAT10/USP7/CHK1 axis might be a plausible therapeutic approach to alleviate renal fibrosis in chronic kidney disease.

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Section: Discussionmentioning

confidence: 99%

Ubiquitin-like protein FAT10 promotes renal fibrosis by stabilizing USP7 to prolong CHK1-mediated G2/M arrest in renal tubular epithelial cells

Shao

Zhang

et al. 2022

Aging

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“…HLA‐F adjacent transcript 10 (FAT10) is a member of the ubiquitin‐like protein family and is also known as ubiquitin D (Xiang et al, 2019). Studies have shown that FAT10 may arrest the cell cycle at the G1‐phase and lead to inhibition of apoptosis (Yi et al, 2020).…”

Section: Involvement Of the Hippo Pathway In Osmentioning

confidence: 99%

The Hippo in the room: Targeting the Hippo signalling pathway for osteosarcoma therapies

Rothzerg

Ingley

Mullin

et al. 2020

Journal Cellular Physiology

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Osteosarcoma (OS) is a primary malignant bone tumour which usually occurs in children and adolescents. OS is primarily a result of chromosomal aberrations, a combination of acquired genetic changes and, hereditary, resulting in the dysregulation of cellular functions. The Hippo signalling pathway regulates cell and tissue growth by modulating cell proliferation, differentiation, and migration in developing organs. Mammalian STE20-like 1/2 (MST1/2) protein kinases are activated by neurofibromatosis type 2, Ras association domain family member 2, kidney and brain protein, or other factors. Interactions between MST1/2 and salvador family WW domain-containing protein 1 activate large tumour suppressor kinase 1/2 proteins, which in turn phosphorylate the downstream Yes-associated protein 1/transcriptional coactivator with PDZ-binding motif (YAP/TAZ). Moreover, dysregulation of this pathway can lead to aberrant cell growth, resulting in tumorigenesis. Interestingly, small molecules targeting the Hippo signalling pathways, through affecting YAP/TAZ cellular localisation and their interaction with members of the TEA/ATTS domain family of transcriptional enhancers are being developed and hold promise for the treatment of OS. This review discusses the existing knowledge about the involvement of the Hippo signalling cascade in OS and highlights several small molecule inhibitors as potential novel therapeutics.

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“… 8 Deregulation of UBD may result in aberrant modifications in apoptosis, cell division, or chromosomal instability, all of which are linked to cancer. 9 Increased studies on UBD in malignancies have emerged in recent years, revealing a link between increased UBD expression and disease development in several tumors, 10 , 11 such as hepatocellular carcinoma, 12 , 13 colon cancer, 14 gastric cancer, 15 oral squamous cell carcinoma, 16 breast cancer, 17 and glioma. 18 However, the role of UBD in rectal cancer had never been explored.…”

Section: Introductionmentioning

confidence: 99%

Upregulated Ubiquitin D is a Favorable Prognostic Indicator for Rectal Cancer Patients Undergoing Preoperative Concurrent Chemoradiotherapy

Chou¹,

Chen²,

Li³

et al. 2022

OTT

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Purpose For locally advanced rectal cancer, neoadjuvant concurrent chemoradiotherapy (CCRT) allows tumor downstaging and makes curative radical proctectomy possible. However, we lack a genetic biomarker to predict cancer prognosis or treatment response. We investigated the association between ubiquitin D (UBD) expression and clinical outcomes in rectal cancer patients receiving CCRT. Patients and Methods We analyzed the genes associated with the protein modification process (GO:0036211) and identified the UBD gene as the most relevant among the top 7 differentially expressed genes associated with CCRT resistance. We collected tissue specimens from 172 rectal cancer patients who had received CCRT followed by a curative proctectomy. We examine the relationship between UBD expression and patient characteristics, pathological findings, and patient survival, such as metastasis-free survival (MeFS) and disease-specific survival. Results Upregulated UBD expression was associated with lower pre-CCRT tumor T stage (P = 0.009), lower post-CCRT tumor T stage (P < 0.001), lower post-CCRT nodal stage (P < 0.001), less vascular invasion (P = 0.015), and better tumor regression (P < 0.001). Using univariate analysis, we found that high UBD expression was correlated with better disease-free survival (DFS) (P < 0.0001), local recurrence-free survival (LRFS) (P < 0.0001) and MeFS (P < 0.0001). Moreover, multivariate analysis demonstrated that high UBD expression was associated with superior DFS (P < 0.001), LRFS (P = 0.01), and MeFS (P = 0.004). Conclusion UBD upregulation was linked to better clinical prognosis, favorable pathological features, and good treatment response in rectal cancer patients undergoing CCRT. These results suggest UBD is a biomarker for rectal cancer.

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FAT10: Function and Relationship with Cancer

Cited by 17 publications

References 73 publications

Ubiquitin-like protein FAT10 promotes renal fibrosis by stabilizing USP7 to prolong CHK1-mediated G2/M arrest in renal tubular epithelial cells

Ubiquitin-like protein FAT10 promotes renal fibrosis by stabilizing USP7 to prolong CHK1-mediated G2/M arrest in renal tubular epithelial cells

The Hippo in the room: Targeting the Hippo signalling pathway for osteosarcoma therapies

Upregulated Ubiquitin D is a Favorable Prognostic Indicator for Rectal Cancer Patients Undergoing Preoperative Concurrent Chemoradiotherapy

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