Functional Characterization of FBXL7 As a Novel Player in Human Cancers

Overview

Journal Cell Death Discov

Date 2022 Jul 29

PMID 35906197

Authors

Yue Wang

Xiao Shen

Longyuan Gong

Yongchao Zhao

Xiufang Xiong

Affiliations

Soon will be listed here.

Abstract

F-box and leucine-rich repeat protein 7 (FBXL7), an F-box protein responsible for substrate recognition by the SKP1-Cullin-1-F-box (SCF) ubiquitin ligases, plays an emerging role in the regulation of tumorigenesis and tumor progression. FBXL7 promotes polyubiquitylation and degradation of diverse substrates and is involved in many biological processes, including apoptosis, cell proliferation, cell migration and invasion, tumor metastasis, DNA damage, glucose metabolism, planar cell polarity, and drug resistance. In this review, we summarize the downstream substrates and upstream regulators of FBXL7. We then discuss its role in tumorigenesis and tumor progression as either an oncoprotein or a tumor suppressor, and further describe its aberrant expression and association with patient survival in human cancers. Finally, we provide future perspectives on validating FBXL7 as a cancer biomarker for diagnosis and prognosis and/or as a potential therapeutic target for anticancer treatment.

Citing Articles

Establishment of a circRNA-regulated E3 ubiquitin ligase signature and nomogram to predict immunotherapeutic efficacy and prognosis in hepatocellular carcinoma.

Wu G, Zhang J, Peng R, Cao J, Tu D, Zhou J Eur J Med Res. 2024; 29(1):318.

PMID: 38858746 PMC: 11163726. DOI: 10.1186/s40001-024-01893-6.

Genome-wide 5-hydroxymethylcytosines in circulating cell-free DNA as noninvasive diagnostic markers for gastric cancer.

Fu Y, Jiang J, Wu Y, Cao D, Jia Z, Zhang Y Gastric Cancer. 2024; 27(4):735-746.

PMID: 38584223 DOI: 10.1007/s10120-024-01493-7.

References

Xiao G, Li Y, Wang M, Li X, Qin S, Sun X . FBXW7 suppresses epithelial-mesenchymal transition and chemo-resistance of non-small-cell lung cancer cells by targeting snai1 for ubiquitin-dependent degradation. Cell Prolif. 2018; 51(5):e12473. PMC: 6528938. DOI: 10.1111/cpr.12473. View

Tang Z, Li C, Kang B, Gao G, Li C, Zhang Z . GEPIA: a web server for cancer and normal gene expression profiling and interactive analyses. Nucleic Acids Res. 2017; 45(W1):W98-W102. PMC: 5570223. DOI: 10.1093/nar/gkx247. View

Xu M, Zhu C, Zhao X, Chen C, Zhang H, Yuan H . Atypical ubiquitin E3 ligase complex Skp1-Pam-Fbxo45 controls the core epithelial-to-mesenchymal transition-inducing transcription factors. Oncotarget. 2014; 6(2):979-94. PMC: 4359269. DOI: 10.18632/oncotarget.2825. View

Forno E, Wang T, Qi C, Yan Q, Xu C, Boutaoui N . DNA methylation in nasal epithelium, atopy, and atopic asthma in children: a genome-wide study. Lancet Respir Med. 2018; 7(4):336-346. PMC: 6441380. DOI: 10.1016/S2213-2600(18)30466-1. View

Zhang X, Feng S, Fan Y, Luo Y, Jin L, Li S . Identifying a Comprehensive ceRNA Network to Reveal Novel Targets for the Pathogenesis of Parkinson's Disease. Front Neurol. 2020; 11:810. PMC: 7417679. DOI: 10.3389/fneur.2020.00810. View

Rodrigues-Campos M, Thompson B . The ubiquitin ligase FbxL7 regulates the Dachsous-Fat-Dachs system in Drosophila. Development. 2014; 141(21):4098-103. PMC: 4302899. DOI: 10.1242/dev.113498. View

Skaar J, Pagan J, Pagano M . SCF ubiquitin ligase-targeted therapies. Nat Rev Drug Discov. 2014; 13(12):889-903. PMC: 4410837. DOI: 10.1038/nrd4432. View

Wang B, Dai T, Sun W, Wei Y, Ren J, Zhang L . Protein N-myristoylation: functions and mechanisms in control of innate immunity. Cell Mol Immunol. 2021; 18(4):878-888. PMC: 7966921. DOI: 10.1038/s41423-021-00663-2. View

Zheng H, Shen M, Zha Y, Li W, Wei Y, Blanco M . PKD1 phosphorylation-dependent degradation of SNAIL by SCF-FBXO11 regulates epithelial-mesenchymal transition and metastasis. Cancer Cell. 2014; 26(3):358-373. PMC: 4159622. DOI: 10.1016/j.ccr.2014.07.022. View

10.

Cornejo-Garcia J, Liou L, Blanca-Lopez N, Dona I, Chen C, Chou Y . Genome-wide association study in NSAID-induced acute urticaria/angioedema in Spanish and Han Chinese populations. Pharmacogenomics. 2013; 14(15):1857-69. DOI: 10.2217/pgs.13.166. View

11.

Li M, Gao F, Yu X, Zhao Q, Zhou L, Liu W . Promotion of ubiquitination-dependent survivin destruction contributes to xanthohumol-mediated tumor suppression and overcomes radioresistance in human oral squamous cell carcinoma. J Exp Clin Cancer Res. 2020; 39(1):88. PMC: 7227341. DOI: 10.1186/s13046-020-01593-z. View

12.

Vinas-Castells R, Beltran M, Valls G, Gomez I, Garcia J, Montserrat-Sentis B . The hypoxia-controlled FBXL14 ubiquitin ligase targets SNAIL1 for proteasome degradation. J Biol Chem. 2009; 285(6):3794-3805. PMC: 2823521. DOI: 10.1074/jbc.M109.065995. View

13.

Tekcham D, Chen D, Liu Y, Ling T, Zhang Y, Chen H . F-box proteins and cancer: an update from functional and regulatory mechanism to therapeutic clinical prospects. Theranostics. 2020; 10(9):4150-4167. PMC: 7086354. DOI: 10.7150/thno.42735. View

14.

Liu Y, Lear T, Iannone O, Shiva S, Corey C, Rajbhandari S . The Proapoptotic F-box Protein Fbxl7 Regulates Mitochondrial Function by Mediating the Ubiquitylation and Proteasomal Degradation of Survivin. J Biol Chem. 2015; 290(19):11843-52. PMC: 4424325. DOI: 10.1074/jbc.M114.629931. View

15.

Jin Y, Shenoy A, Doernberg S, Chen H, Luo H, Shen H . FBXO11 promotes ubiquitination of the Snail family of transcription factors in cancer progression and epidermal development. Cancer Lett. 2015; 362(1):70-82. PMC: 4406488. DOI: 10.1016/j.canlet.2015.03.037. View

16.

Nguyen K, Busino L . The Biology of F-box Proteins: The SCF Family of E3 Ubiquitin Ligases. Adv Exp Med Biol. 2020; 1217:111-122. DOI: 10.1007/978-981-15-1025-0_8. View

17.

Tang L, Ji M, Liang X, Chen D, Liu A, Yang G . Downregulated F-Box/LRR-Repeat Protein 7 Facilitates Pancreatic Cancer Metastasis by Regulating Snail1 for Proteasomal Degradation. Front Genet. 2021; 12:650090. PMC: 8264591. DOI: 10.3389/fgene.2021.650090. View

18.

Vinas-Castells R, Frias A, Robles-Lanuza E, Zhang K, Longmore G, Garcia de Herreros A . Nuclear ubiquitination by FBXL5 modulates Snail1 DNA binding and stability. Nucleic Acids Res. 2013; 42(2):1079-94. PMC: 3902928. DOI: 10.1093/nar/gkt935. View

19.

Rape M . Ubiquitylation at the crossroads of development and disease. Nat Rev Mol Cell Biol. 2017; 19(1):59-70. DOI: 10.1038/nrm.2017.83. View

20.

Nakayama K, Nakayama K . Ubiquitin ligases: cell-cycle control and cancer. Nat Rev Cancer. 2006; 6(5):369-81. DOI: 10.1038/nrc1881. View