<i>Retracted:</i> Ubiquitin ligase <scp>SMURF</scp>1 functions as a prognostic marker and promotes growth and metastasis of clear cell renal cell carcinoma

Ke, Mang; Mo, Licai; Li, Weilin; Zhang, Xianjun; Yu, Hongyuan

doi:10.1002/2211-5463.12204

Cited by 22 publications

(19 citation statements)

References 24 publications

(37 reference statements)

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“…The existence of similar Smurf1-regulated tumor promoting mechanism was also observed in clear cell renal cell carcinoma (ccRCC) cells ( 87 ). This mechanism was associated with the ability of Smurf1 to promote proliferation, migration, and invasion of ccRCC cells.…”

Section: Regulatory Roles Of Smurfs In the Decisive Cellular Processementioning

confidence: 70%

Smurfs in Protein Homeostasis, Signaling, and Cancer

2018

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Protein ubiquitination is an evolutionary conserved highly-orchestrated enzymatic cascade essential for normal cellular functions and homeostasis maintenance. This pathway relies on a defined set of cellular enzymes, among them, substrate-specific E3 ubiquitin ligases (E3s). These ligases are the most critical players, as they define the spatiotemporal nature of ubiquitination and confer specificity to this cascade. Smurf1 and Smurf2 (Smurfs) are the C2-WW-HECT-domain E3 ubiquitin ligases, which recently emerged as important determinants of pivotal cellular processes. These processes include cell proliferation and differentiation, chromatin organization and dynamics, DNA damage response and genomic integrity maintenance, gene expression, cell stemness, migration, and invasion. All these processes are intimately connected and profoundly altered in cancer. Initially, Smurf proteins were identified as negative regulators of the bone morphogenetic protein (BMP) and the transforming growth factor beta (TGF-β) signaling pathways. However, recent studies have extended the scope of Smurfs' biological functions beyond the BMP/TGF-β signaling regulation. Here, we provide a critical literature overview and updates on the regulatory roles of Smurfs in molecular and cell biology, with an emphasis on cancer. We also highlight the studies demonstrating the impact of Smurf proteins on tumor cell sensitivity to anticancer therapies. Further in-depth analyses of Smurfs' biological functions and influences on molecular pathways could provide novel therapeutic targets and paradigms for cancer diagnosis and treatment.

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Section: Regulatory Roles Of Smurfs In the Decisive Cellular Processementioning

confidence: 70%

Smurfs in Protein Homeostasis, Signaling, and Cancer

2018

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“…Numerous studies have demonstrated the oncogenic role of Smurf1 in human cells due to its contributory effects on aberrant degradation of tumor suppressor proteins [10,22,23]. For instance, Xie et al illustrated that Smurf1 was highly expressed in human lung cancer H1299 cells and promoted the ubiquitin dependent degradation of Kruppel-like factor 2 (KLF2), an essential protein in regulation of normal lung development and differentiation [24].…”

Section: Discussionmentioning

confidence: 99%

Smad Ubiquitination Regulatory Factor 1 (Smurf1) Promotes Thyroid Cancer Cell Proliferation and Migration via Ubiquitin-Dependent Degradation of Kisspeptin-1

Yan

Su²,

Song

et al. 2018

Cell Physiol Biochem

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Background/Aims: Thyroid cancer is the most common malignancy in human endocrine system. Smad ubiquitination regulatory factor 1 (Smurf1) is an E3 ubiquitin-protein ligase in ubiquitin-proteasome pathway (UPP) system. This study aimed to investigate the effects of Smurf1 on thyroid cancer proliferation and metastasis, as well as underlying potential mechanism. Methods: The expression levels of Smurf1 in thyroid tumor tissues and thyroid cancer cells were detected by western blotting and qRT-PCR. Then, the effects of up-regulation or down-regulation of Smurf1 on thyroid cancer cell viability, migration, invasion, proliferation and apoptosis were measured using trypan blue exclusion assay, two-chamber migration (invasion) assay, cell colony formation assay and Guava Nexin assay, respectively. The ubiquitination of kisspeptin-1 (KISS-1) was assessed by protein ubiquitination assay. Finally, the effects of KISS-1 overexpression on activity of nuclear factor-kappa B (NF-κB) signaling pathway, as well as thyroid cancer cell viability, migration, invasion, proliferation and apoptosis were also detected, respectively. Results: Smurf1 was highly expressed in thyroid tumor tissues and thyroid cancer cells. Up-regulation of Smurf1 promoted the viability, migration, invasion and proliferation of thyroid cancer cells. Knockdown of Smurf1 had opposite effects. Moreover, smurf1 promoted the ubiquitination of KISS-1. Overexpression of KISS-1 inactivated NF-κB pathway, suppressed thyroid cancer cell viability, migration, invasion and proliferation, and induced cell apoptosis. Conclusion: Up-regulation of Smurf1 exerted important roles in thyroid cancer formation and development by promoting thyroid cancer proliferation and metastasis. The ubiquitin-dependent degradation of KISS-1 induced by Smurf1 and the activation of NF-κB signaling pathway might be involved in this process. Smurf1 could be an effective therapy target and biomarker for thyroid cancer treatment.

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“…Some studies have shown that the phosphatidylinositol 3′-kinase/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR) pathway plays a central role in cell growth, survival, apoptosis, and migration. [12][13][14] Moreover, increasing studies have indicated that PI3K/Akt/mTOR pathway plays an important role in various cancers, including cervical cancer. 15,16 Moreover, ADRA2A is reported to be associated with PI3K/AKT/mTOR signaling pathway in many diseases.…”

Section: Introductionmentioning

confidence: 99%

<p>α2A-Adrenergic Receptor Inhibits the Progression of Cervical Cancer Through Blocking PI3K/AKT/mTOR Pathway</p>

Wang¹,

Guo²,

Dan³

2020

OTT

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The study aimed to investigate the effect of α2A-adrenergic receptor (ADRA2A) on cervical cancer and the potential mechanisms of ADRA2A on phosphatidylinositol 3′kinase/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR) pathway in cervical cancer cells. Methods: In our study, ADRA2A expression was evaluated by analyzing cervical cancer RNA sequencing dataset from the GEPIA. The prognostic values of ADRA2A were evaluated by Kaplan-Meier method using the Cancer Genome Atlas (TCGA) database data. In addition, the expression of ADRA2A in cervical cancer cell lines was detected by qRT-PCR and Western blot. Subsequently, the roles of ADRA2A on cell proliferation, apoptosis, migration, invasion and senescence in HeLa and SiHa cells were evaluated. Moreover, tumorigenesis in nude mice was used to investigate the role of ADRA2A in vivo. We also detected the expression changes of key factors in PI3K/Akt/mTOR pathway after overexpression and silencing of ADRA2A in HeLa and SiHa cells. Results: ADRA2A expression was significantly downregulated in cervical cancer tissues and cell lines. The high expression of ADRA2A was significantly associated with a better prognosis in cervical cancer patients. ADRA2A overexpression significantly suppressed cell proliferation, migration and invasion, and promoted cell senescence and apoptosis in cervical cancer cells. On the contrary, silencing ADRA2A dramatically facilitated cell proliferation, migration and invasion, and inhibited cell senescence and apoptosis in cervical cancer cells. The expressions of p-PI3K, p-AKT and p-mTOR in cervical cancer cells were notably decreased by ADRA2A overexpression and increased by silencing ADRA2A. In addition, we also confirmed that ADRA2A overexpression could suppress the xenograft tumor growth in vivo. Conclusion: Our study demonstrated that ADRA2A could suppress cell proliferation, migration and invasion, as well as promote cell senescence and apoptosis through inhibiting PI3K/Akt/mTOR pathway in cervical cancer.

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Retracted: Ubiquitin ligase SMURF1 functions as a prognostic marker and promotes growth and metastasis of clear cell renal cell carcinoma

Cited by 22 publications

References 24 publications

Smurfs in Protein Homeostasis, Signaling, and Cancer

Smurfs in Protein Homeostasis, Signaling, and Cancer

Smad Ubiquitination Regulatory Factor 1 (Smurf1) Promotes Thyroid Cancer Cell Proliferation and Migration via Ubiquitin-Dependent Degradation of Kisspeptin-1

<p>α2A-Adrenergic Receptor Inhibits the Progression of Cervical Cancer Through Blocking PI3K/AKT/mTOR Pathway</p>

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