FBXW7 in Cancer: What Has Been Unraveled Thus Far?

doi:10.3390/cancers11020246

Review

. 2019 Feb 19;11(2):246.

doi: 10.3390/cancers11020246.

FBXW7 in Cancer: What Has Been Unraveled Thus Far?

Bethsebie Lalduhsaki Sailo¹, Kishore Banik², Sosmitha Girisa³, Devivasha Bordoloi⁴, Lu Fan⁵, Clarissa Esmeralda Halim⁶, Hong Wang⁷, Alan Prem Kumar^{8

9

10

11}, Dali Zheng¹², Xinliang Mao^{13

14}, Gautam Sethi¹⁵, Ajaikumar Bahulayan Kunnumakkara¹⁶

Affiliations

¹ Cancer Biology Laboratory and DBT-AIST International Laboratory for Advanced Biomedicine (DAILAB), Department of Biosciences and Bioengineering, Indian Institute of Technology Guwahati, Guwahati, Assam-781039, India. bethsailo@gmail.com.
² Cancer Biology Laboratory and DBT-AIST International Laboratory for Advanced Biomedicine (DAILAB), Department of Biosciences and Bioengineering, Indian Institute of Technology Guwahati, Guwahati, Assam-781039, India. kishore.banik@iitg.ernet.in.
³ Cancer Biology Laboratory and DBT-AIST International Laboratory for Advanced Biomedicine (DAILAB), Department of Biosciences and Bioengineering, Indian Institute of Technology Guwahati, Guwahati, Assam-781039, India. sosmi176106101@iitg.ac.
⁴ Cancer Biology Laboratory and DBT-AIST International Laboratory for Advanced Biomedicine (DAILAB), Department of Biosciences and Bioengineering, Indian Institute of Technology Guwahati, Guwahati, Assam-781039, India. devivasha@iitg.ac.in.
⁵ Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117 600, Singapore. phcfanl@nus.edu.sg.
⁶ Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117 600, Singapore. phsceh@nus.edu.sg.
⁷ Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117 600, Singapore. snrwh@nus.edu.sg.
⁸ Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117 600, Singapore. csiapk@nus.edu.sg.
⁹ Cancer Science Institute of Singapore, National University of Singapore, Singapore 117 600, Singapore. csiapk@nus.edu.sg.
¹⁰ Medical Science Cluster, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117 600, Singapore. csiapk@nus.edu.sg.
¹¹ Curtin Medical School, Faculty of Health Sciences, Curtin University, 6845, Perth WA, Australia. csiapk@nus.edu.sg.
¹² The School of Stomatology, Fujian Medical University, 1 Xue Yuan Road, University Town, FuZhou Fujian 350108, China. dalizheng@hotmail.com.
¹³ Institute of Clinical Pharmacology, Guangzhou University of Chinese Medicine, 12 Jichang Road, Baiyun District, Guangzhou 510405, China. xinliangmao@suda.edu.cn.
¹⁴ Department of Pharmacology, College of Pharmaceutical Sciences, Soochow University, 199 Ren'ai Road, Suzhou, Jiangsu 215123, China. xinliangmao@suda.edu.cn.
¹⁵ Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117 600, Singapore. kunnumakkara@iitg.ac.in.
¹⁶ Cancer Biology Laboratory and DBT-AIST International Laboratory for Advanced Biomedicine (DAILAB), Department of Biosciences and Bioengineering, Indian Institute of Technology Guwahati, Guwahati, Assam-781039, India. ajai78@gmail.com.

PMID: 30791487
PMCID: PMC6406609
DOI: 10.3390/cancers11020246

Review

FBXW7 in Cancer: What Has Been Unraveled Thus Far?

Bethsebie Lalduhsaki Sailo et al. Cancers (Basel). 2019.

. 2019 Feb 19;11(2):246.

doi: 10.3390/cancers11020246.

Authors

Affiliations

¹ Cancer Biology Laboratory and DBT-AIST International Laboratory for Advanced Biomedicine (DAILAB), Department of Biosciences and Bioengineering, Indian Institute of Technology Guwahati, Guwahati, Assam-781039, India. bethsailo@gmail.com.
² Cancer Biology Laboratory and DBT-AIST International Laboratory for Advanced Biomedicine (DAILAB), Department of Biosciences and Bioengineering, Indian Institute of Technology Guwahati, Guwahati, Assam-781039, India. kishore.banik@iitg.ernet.in.
³ Cancer Biology Laboratory and DBT-AIST International Laboratory for Advanced Biomedicine (DAILAB), Department of Biosciences and Bioengineering, Indian Institute of Technology Guwahati, Guwahati, Assam-781039, India. sosmi176106101@iitg.ac.
⁴ Cancer Biology Laboratory and DBT-AIST International Laboratory for Advanced Biomedicine (DAILAB), Department of Biosciences and Bioengineering, Indian Institute of Technology Guwahati, Guwahati, Assam-781039, India. devivasha@iitg.ac.in.
⁵ Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117 600, Singapore. phcfanl@nus.edu.sg.
⁶ Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117 600, Singapore. phsceh@nus.edu.sg.
⁷ Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117 600, Singapore. snrwh@nus.edu.sg.
⁸ Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117 600, Singapore. csiapk@nus.edu.sg.
⁹ Cancer Science Institute of Singapore, National University of Singapore, Singapore 117 600, Singapore. csiapk@nus.edu.sg.
¹⁰ Medical Science Cluster, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117 600, Singapore. csiapk@nus.edu.sg.
¹¹ Curtin Medical School, Faculty of Health Sciences, Curtin University, 6845, Perth WA, Australia. csiapk@nus.edu.sg.
¹² The School of Stomatology, Fujian Medical University, 1 Xue Yuan Road, University Town, FuZhou Fujian 350108, China. dalizheng@hotmail.com.
¹³ Institute of Clinical Pharmacology, Guangzhou University of Chinese Medicine, 12 Jichang Road, Baiyun District, Guangzhou 510405, China. xinliangmao@suda.edu.cn.
¹⁴ Department of Pharmacology, College of Pharmaceutical Sciences, Soochow University, 199 Ren'ai Road, Suzhou, Jiangsu 215123, China. xinliangmao@suda.edu.cn.
¹⁵ Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117 600, Singapore. kunnumakkara@iitg.ac.in.
¹⁶ Cancer Biology Laboratory and DBT-AIST International Laboratory for Advanced Biomedicine (DAILAB), Department of Biosciences and Bioengineering, Indian Institute of Technology Guwahati, Guwahati, Assam-781039, India. ajai78@gmail.com.

PMID: 30791487
PMCID: PMC6406609
DOI: 10.3390/cancers11020246

Abstract

: The FBXW7 (F-box with 7 tandem WD40) protein encoded by the gene FBXW7 is one of the crucial components of ubiquitin ligase called Skp1-Cullin1-F-box (SCF) complex that aids in the degradation of many oncoproteins via the ubiquitin-proteasome system (UPS) thus regulating cellular growth. FBXW7 is considered as a potent tumor suppressor as most of its target substrates can function as potential growth promoters, including c-Myc, Notch, cyclin E, c-JUN, and KLF5. Its regulators include p53, C/EBP-δ, Numb, microRNAs, Pin 1, Hes-5, BMI1, Ebp2. Mounting evidence has indicated the involvement of aberrant expression of FBXW7 for tumorigenesis. Moreover, numerous studies have also shown its role in cancer cell chemosensitization, thereby demonstrating the importance of FBXW7 in the development of curative cancer therapy. This comprehensive review emphasizes on the targets, functions, regulators and expression of FBXW7 in different cancers and its involvement in sensitizing cancer cells to chemotherapeutic drugs.

Keywords: FBXW7; SCF complex; cancer; chemoresistance; chemosensitization; mutations; tumor suppressor.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

**Figure 3**
Regulators and targets of FBXW7 in cancer.

See this image and copyright information in PMC

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[1] Ferlay J., Soerjomataram I., Dikshit R., Eser S., Mathers C., Rebelo M., Parkin D.M., Forman D., Bray F. Cancer incidence and mortality worldwide: Sources, methods and major patterns in GLOBOCAN 2012. Int. J. Cancer. 2015;136:E359–E386. doi: 10.1002/ijc.29210. - DOI - PubMed

[2] Ferlay J., Soerjomataram I., Dikshit R., Eser S., Mathers C., Rebelo M., Parkin D.M., Forman D., Bray F. Cancer incidence and mortality worldwide: Sources, methods and major patterns in GLOBOCAN 2012. Int. J. Cancer. 2015;136:E359–E386. doi: 10.1002/ijc.29210. - DOI - PubMed

[3] Zhao E., Maj T., Kryczek I., Li W., Wu K., Zhao L., Wei S., Crespo J., Wan S., Vatan L., et al. Cancer mediates effector T cell dysfunction by targeting microRNAs and EZH2 via glycolysis restriction. Nat. Immunol. 2016;17:95–103. doi: 10.1038/ni.3313. - DOI - PMC - PubMed

[4] Zhao E., Maj T., Kryczek I., Li W., Wu K., Zhao L., Wei S., Crespo J., Wan S., Vatan L., et al. Cancer mediates effector T cell dysfunction by targeting microRNAs and EZH2 via glycolysis restriction. Nat. Immunol. 2016;17:95–103. doi: 10.1038/ni.3313. - DOI - PMC - PubMed

[5] Shabnam B., Padmavathi G., Banik K., Girisa S., Monisha J., Sethi G., Fan L., Wang L., Mao X., Kunnumakkara A.B. Sorcin a Potential Molecular Target for Cancer Therapy. Transl. Oncol. 2018;11:1379–1389. doi: 10.1016/j.tranon.2018.08.015. - DOI - PMC - PubMed

[6] Shabnam B., Padmavathi G., Banik K., Girisa S., Monisha J., Sethi G., Fan L., Wang L., Mao X., Kunnumakkara A.B. Sorcin a Potential Molecular Target for Cancer Therapy. Transl. Oncol. 2018;11:1379–1389. doi: 10.1016/j.tranon.2018.08.015. - DOI - PMC - PubMed

[7] Ranaware A.M., Banik K., Deshpande V., Padmavathi G., Roy N.K., Sethi G., Fan L., Kumar A.P., Kunnumakkara A.B. Magnolol: A Neolignan from the Magnolia Family for the Prevention and Treatment of Cancer. Int. J. Mol. Sci. 2018;19:2362. doi: 10.3390/ijms19082362. - DOI - PMC - PubMed

[8] Ranaware A.M., Banik K., Deshpande V., Padmavathi G., Roy N.K., Sethi G., Fan L., Kumar A.P., Kunnumakkara A.B. Magnolol: A Neolignan from the Magnolia Family for the Prevention and Treatment of Cancer. Int. J. Mol. Sci. 2018;19:2362. doi: 10.3390/ijms19082362. - DOI - PMC - PubMed

[9] Banik K., Harsha C., Bordoloi D., Lalduhsaki Sailo B., Sethi G., Leong H.C., Arfuso F., Mishra S., Wang L., Kumar A.P., et al. Therapeutic potential of gambogic acid, a caged xanthone, to target cancer. Cancer Lett. 2018;416:75–86. doi: 10.1016/j.canlet.2017.12.014. - DOI - PubMed

[10] Banik K., Harsha C., Bordoloi D., Lalduhsaki Sailo B., Sethi G., Leong H.C., Arfuso F., Mishra S., Wang L., Kumar A.P., et al. Therapeutic potential of gambogic acid, a caged xanthone, to target cancer. Cancer Lett. 2018;416:75–86. doi: 10.1016/j.canlet.2017.12.014. - DOI - PubMed

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FBXW7 in Cancer: What Has Been Unraveled Thus Far?

Affiliations

FBXW7 in Cancer: What Has Been Unraveled Thus Far?

Authors

Affiliations

Abstract

Conflict of interest statement

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References

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