Regulating Fbw7 on the road to cancer

Xu, Wen-Shan; Taranets, Lyudmyla; Popov, Nikita

doi:10.1016/j.semcancer.2015.09.005

Cited by 33 publications

(39 citation statements)

References 111 publications

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“…Breast cancer patients with a low level of FBXW7 expression survive longer than those with a high level. Although Fbxw7 was first identified as a tumor suppressor (41), recent studies have shown that it can also play an oncogenic role depending on the cellular context (42,43). Our present results showed that Fbxw7 ablation induces quiescent tumor cells to enter the cell cycle and thereby renders them susceptible to conventional chemotherapy in 2 independent mouse models.…”

Section: Resultssupporting

confidence: 51%

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Prevention of cancer dormancy by Fbxw7 ablation eradicates disseminated tumor cells

et al. 2019

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Section: Resultssupporting

confidence: 51%

“…These results thus suggested that p53 is not a direct upstream regulator of FBXW7 expression in this context. Fbxw7 exists in several isoforms: Fbxw7β, Fbxw7γ, and the major isoform Fbxw7α (42). Various stress conditions have been shown to specifically increase Fbxw7β expression, largely in a p53-dependent manner (54).…”

Section: Discussionmentioning

confidence: 99%

Prevention of cancer dormancy by Fbxw7 ablation eradicates disseminated tumor cells

et al. 2019

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“…58 Cyclin E2 is indirectly targeted by miR-223, and miR-223, in turn, targets FBXW7 that is associated with the degradation of cyclin E2 through ubiquitination. 59,60 Further, cyclin E2 is inhibited by P27 and P57, which are critical negative regulators of G1/S progression, and the former is regulated by miR-21 and the latter is regulated by miR-222. 30,61-63 miR-148b functions as a tumour suppressor by targeting AMPKα1, and AMPKα1 functions in normal cells as a central regulator of lipid and glucose metabolism.…”

Section: Cell Cyclementioning

confidence: 99%

MicroRNA in pancreatic cancer

2016

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Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal malignancies. Patients with PDAC are often asymptomatic, and many have lymph node and distant metastases as well as vessel invasion upon diagnosis. Surgery and current chemotherapy have limited efficacy for improving prognosis, which accounts for overall median survival of 8.6 months and a 9.7% 5-year survival rate. MicroRNAs (miRNAs) are attracting increasing attention because of their association with tumour progression. At least 50% of miRNAs that are aberrantly expressed in tumours have important roles as post-transcriptional regulators and exhibit oncogenic or tumour suppressive activities by directly binding to their target messenger RNAs. Various techniques are available to identify miRNAs that are differentially expressed in cancerous vs normal tissues. In this review, we summarise the miRNA profiles of normal pancreatic tissue and cancer tissue of patients with PDACs and characterise the expression of miRNAs associated with tumour progression. Further, we highlight the target genes and signalling pathways of miRNAs that are aberrantly expressed in PDACs. This knowledge may lead to the development of preventive and therapeutic strategies for treating this deadly disease.

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“…Usually, FBXW7 targets substrates by recognizing a short, phosphothreonine-containing motif known as Cdc4 phosphodegron (CPD) (29,30). Interestingly, the sequence surrounding Ser305 and Ser309 in fetuin-A protein conforms to a highly conserved CPD found in other well-established FBXW7 substrates ( Supplementary Fig.…”

Section: Fbxw7 Promotes Ubiquitination and Degradation Of Fetuin-amentioning

confidence: 99%

Hepatic F-Box Protein FBXW7 Maintains Glucose Homeostasis Through Degradation of Fetuin-A

Zhao

Xiong

et al. 2018

Diabetes

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Type 2 diabetes mellitus (T2DM) has become one of the most serious and long-term threats to human health. However, the molecular mechanism that links obesity to insulin resistance remains largely unknown. Here, we show that F-box and WD repeat domain-containing 7 (FBXW7), an E3 ubiquitin protein ligase, is markedly downregulated in the liver of two obese mouse models and obese human subjects. We further identify a functional low-frequency human FBXW7 coding variant (p.Ala204Thr) in the Chinese population, which is associated with elevated blood glucose and T2DM risk. Notably, mice with liver-specific knockout of FBXW7 develop hyperglycemia, glucose intolerance, and insulin resistance even on a normal chow diet. Conversely, overexpression of FBXW7 in the liver not only prevents the development of high-fat diet-induced insulin resistance but also attenuates the disease signature of obese mice. Mechanistically, FBXW7 directly binds to hepatokine fetuin-A to induce its ubiquitination and subsequent proteasomal degradation, comprising an important mechanism maintaining glucose homeostasis. Thus, we provide evidence showing a beneficial role of FBXW7 in glucose homeostasis.

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Regulating Fbw7 on the road to cancer

Cited by 33 publications

References 111 publications

Prevention of cancer dormancy by Fbxw7 ablation eradicates disseminated tumor cells

Prevention of cancer dormancy by Fbxw7 ablation eradicates disseminated tumor cells

MicroRNA in pancreatic cancer

Hepatic F-Box Protein FBXW7 Maintains Glucose Homeostasis Through Degradation of Fetuin-A

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