TRIM14 regulates cell proliferation and invasion in osteosarcoma via promotion of the AKT signaling pathway

Xu, Guo; Guo, Yongfei; Xu, Dabo; Wang, Yi; Shen, Yan; Wang, Feifei; Lv, Yuanyuan; Song, Frank M.; Jiang, Dawei; Zhang, Yinquan; Lou, Yu; Meng, Yake; Yang, Yue; Kang, Yifan

doi:10.1038/srep42411

Cited by 60 publications

(58 citation statements)

References 29 publications

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“…Wang et al had reported that TRIM14 overexpression induced EMT and resulted in the formation of cancer‐initiating cells and acquisition of a chemoresistant phenotype by oral tongue squamous cell cancer. TRIM14 was further reported to enhance migration and invasion of osteosarcoma cells and gastric cancer cells by regulating EMT transition via activation of the Akt signaling pathway, which may correspond to the attainment of CSC‐like phenotype. Similar to TRIM27, the exact molecular mode of TRIM14 action in Akt signaling promotion requires further investigation, because neither TRIM14 nor TRIM27 can phosphorylate Akt and other downstream targets.…”

Section: The Engagement Of Specific Trims In Stem Cell Maintenancementioning

confidence: 99%

“…However, for several TRIMs, the molecular mode of action is yet not fully understood and the data suggest the participation of additional factors. 36,38,39,48 Similarly, TRIM-mediated regulation of core pluripotency transcription factor machinery is based on the E3 ubiquitin ligase activity (mediated by the RING domain) 32,55,60 or the ability to form a complex and stabilize specific transcription factors 14,50,51 (unfortunately, it has not been precisely defined whether the TRIM motif is always required for protein-protein interactions).…”

Section: Other Trim Family Members Potentially Involved In the Regumentioning

confidence: 99%

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The role of TRIM family proteins in the regulation of cancer stem cell self-renewal

et al. 2019

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The tripartite-motif (TRIM) family of proteins represents one of the largest classes of putative single protein RING-finger E3 ubiquitin ligases. The members of this family are characterized by an N-terminal TRIM motif containing one RING-finger domain, one or two zinc-finger domains called B boxes (B1 box and B2 box), and a coiled-coil region.The TRIM motif can be found in isolation or in combination with a variety of C-terminal domains, and based on C-terminus, TRIM proteins are classified into 11 distinct groups.Because of the complex nature of TRIM proteins, they are implicated in a variety of cellular functions and biological processes, including regulation of cell proliferation, cell division and developmental processes, cancer transformation, regulation of cell metabolism, autophagocytosis, modification of chromatin status, regulation of gene transcription, post-translational modifications, and interactions with pathogens. Here, we demonstrate the specific activities of TRIM family proteins that contribute to the cancer stem cell phenotype. A growing body of evidence demonstrates that several TRIM members guarantee the acquisition of stem cell properties and the ability to sustain stem-like phenotype by cancer cells using distinct mechanisms. For other members, further work is needed to understand their full contribution to stem cell self-renewal.Identification of TRIM proteins that possess the potential to serve as therapeutic targets may result in the development of new therapeutic strategies. Finally, these strategies may result in the disruption of the machinery of stemness acquisition, which may prevent tumor growth, progression, and overcome the resistance to anticancer therapies. K E Y W O R D Scancer, pluripotency, RING, self-renewal, stem cells, TRIM

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Section: The Engagement Of Specific Trims In Stem Cell Maintenancementioning

confidence: 99%

Section: Other Trim Family Members Potentially Involved In the Regumentioning

confidence: 99%

The role of TRIM family proteins in the regulation of cancer stem cell self-renewal

et al. 2019

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“…TRIM14 promotes breast cancer cell proliferation by inhibiting apoptosis [15]. TRIM14 regulates cell proliferation and invasion in osteosarcoma via promotion of the AKT signaling pathway [16].However, the expression levels and biological functions of TRIM14 in glioblastoma remain to be elucidated.…”

Section: Introductionmentioning

confidence: 99%

Tripartite motif-containing 14 (TRIM14) promotes epithelial-mesenchymal transition via ZEB2 in glioblastoma cells

Feng

Cai

et al. 2019

J Exp Clin Cancer Res

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Background: Several members of the tripartite motif-containing (TRIM) protein family have been reported to serve as vital regulators of tumorigenesis. Recent studies have demonstrated an oncogenic role of TRIM 14 in multiple human cancers; however, the importance of this protein in glioblastoma remains to be elucidated. Methods: The expression levels of TRIM14 were analyzed in a series of database and were examined in a variety of glioblastoma cell lines. Two independent TRIM14 shRNA were transfected into LN229 and U251 cells, and the effect of TRIM14 depletion was confirmed. Transwell assay and wound healing assay assay were carried out to assess the effect of TRIM14 depletion on glioblastoma cell invasion and migration. Western blotting was performed to screen the downstream gene of TRIM14. The stability analysis and Ubiquitylation assays and Orthotopic xenograft studies were also performed to investigate the role of TRIM14 and the relationship with downstream gene. Human glioblastoma tissues were obtained and immunohistochemical staining were carried out to confirm the clinical significance of TRIM14. Results: In this study, we showed that TRIM14 was upregulated in human glioblastoma specimens and cell lines, and correlated with glioblastoma progression and shorter patient survival times. Functional experiments showed that decreased TRIM14 expression reduced glioblastoma cell invasion and migration. Furthermore, we identified that zinc finger E-box binding homeobox 2 (ZEB2), a transcription factor involved in epithelial-mesenchymal transition, is a downstream target of TRIM14. Further investigation revealed that TRIM14 inactivation significantly facilitated ZEB2 ubiquitination and proteasomal degradation, which led to aggressive invasion and migration. Our findings provide insight into the specific biological role of TRIM14 in tumor invasion.Conclusions: Our findings provide insight into the specific biological role of TRIM14 in tumor invasion, and suggest that targeting the TRIM14/ZEB2 axis might be a novel therapeutic approach for blocking glioblastoma.

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“…In addition, the process known as “cadherin switching” (downregulation of E-cadherin and upregulation of mesenchymal cadherins such as N-cadherin [28]) and the accumulation of β-catenin have also been associated with EMT [29]. Previous studies have revealed the increased EMT characteristics in OS cells and demonstrated the involvement of EMT in OS invasiveness and migration [30–33]. In our study, the decreased invasive ability of the U2OS cell line induced by the depletion of SOX3 prompted us to investigate whether SOX3 is involved in EMT.…”

Section: Discussionmentioning

confidence: 99%

Sex-determining region Y-box protein 3 induces epithelial-mesenchymal transition in osteosarcoma cells via transcriptional activation of Snail1

Qiu

Chen

Shen

et al. 2017

J Exp Clin Cancer Res

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BackgroundThe transcription factor sex-determining region Y-box protein 3 (SOX3) plays important roles in various types of cancer. However, its expression and function have not yet been elucidated in osteosarcoma (OS).MethodsThe expression levels of SOX3 in OS tissues and OS cell lines were determined by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot analysis. The effects of SOX3 expression on OS cell biological traits were investigated by overexpressing and downregulating SOX3 protein. The expression of epithelial-mesenchymal transition (EMT) markers and transcription factors associated with EMT (EMT-TFs), were detected simultaneously. The mechanism underlying SOX3-mediated Snail1 expression was further investigated.ResultsSOX3 was upregulated in human OS tissues. SOX3 overexpression promoted the EMT, migration and invasion in OS cells. The downregulation of SOX3 resulted in opposing effects. Furthermore, SOX3 upregulation enhanced the expression of the transcriptional repressor Snail1 by binding to its promoter region. Additionally, a positive correlation among the expression of SOX3, Snail1, and E-cadherin was demonstrated in human OS tissues.ConclusionsSOX3 promotes migration, invasiveness, and EMT in OS cells via transcriptional activation of Snail1 expression, suggesting that SOX3 is a novel regulator of EMT in OS and may serve as a therapeutic target for the treatment of OS metastasis.

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TRIM14 regulates cell proliferation and invasion in osteosarcoma via promotion of the AKT signaling pathway

Cited by 60 publications

References 29 publications

The role of TRIM family proteins in the regulation of cancer stem cell self-renewal

The role of TRIM family proteins in the regulation of cancer stem cell self-renewal

Tripartite motif-containing 14 (TRIM14) promotes epithelial-mesenchymal transition via ZEB2 in glioblastoma cells

Sex-determining region Y-box protein 3 induces epithelial-mesenchymal transition in osteosarcoma cells via transcriptional activation of Snail1

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