The Ubiquitin-like Protein FAT10 Stabilizes eEF1A1 Expression to Promote Tumor Proliferation in a Complex Manner

Liu, Xiuxia; Chen, Leifeng; Jin, Ge; Yan, Chen; Huang, Zixi; Hu, Jinwen; Wen, Chongyu; Li, Ming; Huang, Da; Qiu, Yumin; Hao, Haibin; Yuan, Rongfa; Lei, Jun; Yu, Xianjun; Shao, Jianghua

doi:10.1158/0008-5472.can-15-3118

Cited by 60 publications

(69 citation statements)

References 44 publications

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“…Recently, we showed for the first time that FAT10 stabilized substrate expression by inhibiting ubiquitination of the substrate [13]. In that study, we demonstrated that FAT10 and Ub competitively bound to the substrate to form FAT10- and Ub-substrate complexes; FAT10 overexpression decreased Ub-substrate complex levels and increased FAT10-substrate complex levels [12]. In this study, we provide evidence that FAT10 also stabilizes Survivin and thus increases Survivin expression in BC cells.…”

Section: Discussionsupporting

confidence: 55%

“…We previously found that FAT10 stabilizes substrates by competing with ubiquitin (Ub) for binding, ultimately decreasing substrate ubiquitination [12, 13]. Thus, we hypothesized that competition between FAT10 and Ub for Survivin binding decreases the ubiquitination and degradation of Survivin in BC cells.…”

Section: Resultsmentioning

confidence: 99%

“…FAT10 expression is elevated in liver cancer, stomach cancer, glioma, and other cancer tissues [6, 10, 11]. We recently demonstrated that FAT10 protein is expressed in many tumor cells, and high FAT10 levels were associated with increased proliferation in hepatocellular carcinoma, colon cancer, and cervical carcinoma cells [12, 13]. However, the role of FAT10 expression in BC cells remains unclear.…”

Section: Introductionmentioning

confidence: 99%

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Ubiquitin-like protein FAT10 promotes bladder cancer progression by stabilizing survivin

et al. 2016

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Human HLA-F adjacent transcript 10 (FAT10) is a member of the ubiquitin-likemodifier family of proteins, which have been implicated in cancer development. In addition, the Survivin protein promotes proliferation in bladder cancer (BC). In this study, we explored the link between FAT10 and Survivin. FAT10 expression was dramatically up-regulated in BC tissue samples, and Kaplan-Meier survival analysis revealed that BC patients with high FAT10 expression had shorter overall survival than those with low FAT10 expression. Moreover, RNAi-mediated FAT10 knockdown decreased Survivin protein levels and inhibited BC proliferation both in vitro and in vivo. FAT10 directly bound to and stabilized Survivin protein, thereby promoting cancer cell proliferation by inhibiting ubiquitin-mediated degradation. These results reveal a novel mechanism by which FAT10 promotes tumor proliferation by directly stabilizing Survivin protein in BC.

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Section: Discussionsupporting

confidence: 55%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Ubiquitin-like protein FAT10 promotes bladder cancer progression by stabilizing survivin

et al. 2016

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“…Previous studies of FAT10 have mainly focused on its substrate‐degrading function . We previously reported that FAT10 can stabilize its substrate to promote the progression of tumors, including HCC . We found that FAT10 stabilizes β‐catenin protein by inhibiting its ubiquitination and degradation, thus promoting HCC cell invasion and metastasis .…”

mentioning

confidence: 90%

“…Recently, multiple studies have found that abnormal FAT10 expression is closely related to the occurrence and development of tumors. FAT10 is highly expressed in various tumors, including hepatocellular carcinoma (HCC), and closely related to tumor proliferation, invasion and metastasis, and prognosis . Therefore, FAT10 is considered an oncogene.…”

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confidence: 99%

Human Leukocyte Antigen F Locus Adjacent Transcript 10 Overexpression Disturbs WISP1 Protein and mRNA Expression to Promote Hepatocellular Carcinoma Progression

et al. 2018

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Recently, studies on transcriptome-proteome relationships have revealed mRNA/protein expression discordance for certain genes and speculated that protein posttranslational modification (PTM) may be involved. However, there is currently no evidence to support this hypothesis. Wnt-induced secreted protein-1 (WISP1) is the downstream target gene of β-catenin and plays an important role in tumorigenesis and progression, but the expression and role of WISP1 in different tumor types are controversial. Here, we first confirmed that WISP1 protein expression was significantly down-regulated in hepatocellular carcinoma (HCC) tissue and could be an independent predictor of poor prognosis for patients with HCC. In vivo and in vitro evidence was provided that WISP1 can suppress HCC cell proliferation. Further studies have found that low WISP1 protein expression was related to expression of human leukocyte antigen F locus adjacent transcript 10 (FAT10), a specific ubiquitin-like protein with both degradation and stabilization functions, which plays an important role in PTM. FAT10 overexpression facilitated WISP1 degradation by FAT10ylation to decrease WISP1 protein expression, thus promoting HCC proliferation. Interestingly, we found and demonstrated that FAT10 overexpression could result in WISP1 protein/mRNA expression discordance, with protein expression decreasing while mRNA expression increased. The underlying mechanism is that FAT10 exerts substrate stabilization and degradation functions simultaneously, while FAT10 overexpression promotes WISP1 mRNA expression by stabilizing β-catenin and directly degrades WISP1 protein. Conclusion: Our study demonstrated that overexpression of FAT10 results in expression discordance between WISP1 protein and mRNA, thereby promoting HCC progression by down-regulating WISP1 protein expression.

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eEF1A1 promotes colorectal cancer progression and predicts poor prognosis of patients

et al. 2022

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Colorectal cancer (CRC) is a major leading cause of cancer mortality worldwide in which dysregulated protein synthesis plays an etiologic role. The eukaryotic elongation factor 1 A1 (eEF1A1) exerts significant effects on protein synthesis by contributing to peptide chain extension. Whereas its role in CRC remains to be investigated. In this study, we found that the mRNA and protein levels of eEF1A1 were significantly upregulated in CRC cell lines and tissues. Elevated expression of eEF1A1 was correlated with shorter overall survival in 94 CRC patients. The inhibition of proliferation and cell cycle block were observed in CRC cells after eEF1A1 downregulation. Mechanistically, weighted gene correlation network analysis and further Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis suggested that mitogen‐activated protein kinases (MAPKs) signaling pathways were significantly enriched in high‐eEF1A1 expression group, and the levels of phosphorylated p38/JNK/ERK MAPK were dramatically decreased after eEF1A1 downregulation. Overexpression of eEF1A1 in CRC correlated with a poor prognosis. Collectively, this study determined the oncogenic role of eEF1A1 in CRC proliferation and tumorigenesis. eEF1A1 might be a promising therapeutic target and prognostic biomarker in CRC.

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The Ubiquitin-like Protein FAT10 Stabilizes eEF1A1 Expression to Promote Tumor Proliferation in a Complex Manner

Cited by 60 publications

References 44 publications

Ubiquitin-like protein FAT10 promotes bladder cancer progression by stabilizing survivin

Ubiquitin-like protein FAT10 promotes bladder cancer progression by stabilizing survivin

Human Leukocyte Antigen F Locus Adjacent Transcript 10 Overexpression Disturbs WISP1 Protein and mRNA Expression to Promote Hepatocellular Carcinoma Progression

eEF1A1 promotes colorectal cancer progression and predicts poor prognosis of patients

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