The two faces of FBW7 in cancer drug resistance

Zhiwei Wang, Hidefumi Fukushima, Daming Gao, Hiroyuki Inuzuka, Lixin Wan, Alan W. Lau, Pengda Liu, Wenyi Wei

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

Chemotherapy is an important therapeutic approach for cancer treatment. However, drug resistance is an obstacle that often impairs the successful use of chemotherapies. Therefore, overcoming drug resistance would lead to better therapeutic outcomes for cancer patients. Recently, studies by our own and other groups have demonstrated that there is an intimate correlation between the loss of the F-box and WD repeat domain-containing 7 (FBW7) tumor suppressor and the incurring drug resistance. While loss of FBW7 sensitizes cancer cells to certain drugs, FBW7-/- cells are more resistant to other types of chemotherapies. FBW7 exerts its tumor suppressor function by promoting the degradation of various oncoproteins that regulate many cellular processes, including cell cycle progression, cellular metabolism, differentiation, and apoptosis. Since loss of the FBW7 tumor suppressor is linked to drug resistance, FBW7 may represent a novel therapeutic target to increase drug sensitivity of cancer cells to conventional chemotherapeutics. This paper thus focuses on the new functional aspects of FBW7 in drug resistance. The ubiquitin ligase FBW7 acts as a tumor suppressor by targeting various oncogenic proteins for ubiquitination. Furthermore, loss of FBW7 is linked to drug resistance and this protein may therefore represent a novel therapeutic target to increase drug sensitivity of cancer cells to conventional chemotherapies.

Original languageEnglish
Pages (from-to)851-859
Number of pages9
JournalBioEssays
Volume33
Issue number11
DOIs
Publication statusPublished - 2011 Nov 1

Keywords

  • Cancer
  • Drug resistance
  • FBW7
  • Mcl-1
  • P53
  • Tumor suppressor

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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  • Cite this

    Wang, Z., Fukushima, H., Gao, D., Inuzuka, H., Wan, L., Lau, A. W., Liu, P., & Wei, W. (2011). The two faces of FBW7 in cancer drug resistance. BioEssays, 33(11), 851-859. https://doi.org/10.1002/bies.201100101