2012
DOI: 10.1186/1471-2407-12-541
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The downregulation of Mcl-1 via USP9X inhibition sensitizes solid tumors to Bcl-xl inhibition

Abstract: BackgroundIt has been shown in many solid tumors that the overexpression of the pro-survival Bcl-2 family members Bcl-xL and Mcl-1 confers resistance to a variety of chemotherapeutic agents. Mcl-1 is a critical survival protein in a variety of cell lineages and is critically regulated via ubiquitination.MethodsThe Mcl-1, Bcl-xL and USP9X expression patterns in human lung and colon adenocarcinomas were evaluated via immunohistochemistry. Interaction between USP9X and Mcl-1 was demonstrated by immunoprecipitatio… Show more

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Cited by 77 publications
(75 citation statements)
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“…Identifying SNPs that are associated with cancer and chemosensitivity may therefore be useful in the generation of personalized cancer diagnostic and therapeutic approaches. Numerous studies have shown that Bcl-xl status is associated with the chemosensitivity of cancer cells (32,33). In the present study, it was found that the SNP (rs3208684) A>C variation in the Bcl-xl 3'UTR disrupted the interaction between the let-7 precursor miRNA and Bcl-xl, thus upregulating Bcl-xl expression and Bcl-xl-mediated 5-FU resistance.…”
Section: Let-7b Mirna Binding Site Polymorphism In the Bcl-xl 3'utr Dsupporting
confidence: 48%
“…Identifying SNPs that are associated with cancer and chemosensitivity may therefore be useful in the generation of personalized cancer diagnostic and therapeutic approaches. Numerous studies have shown that Bcl-xl status is associated with the chemosensitivity of cancer cells (32,33). In the present study, it was found that the SNP (rs3208684) A>C variation in the Bcl-xl 3'UTR disrupted the interaction between the let-7 precursor miRNA and Bcl-xl, thus upregulating Bcl-xl expression and Bcl-xl-mediated 5-FU resistance.…”
Section: Let-7b Mirna Binding Site Polymorphism In the Bcl-xl 3'utr Dsupporting
confidence: 48%
“…5 Usp9x was also recently shown to suppress chemotherapy, radiotherapy, and targeted therapy in several tumor types through its regulation of Mcl-1 and other proteins. 6,7 Mcl-1 is essential for tumor cell survival, and high levels are noted in patients with drug-resistant MM. 8 By using proteomics, ubiquitinated Mcl-1 was recently shown to be bound and deubiquitinated by Usp9x, thus preventing its destruction by the proteasome.…”
Section: Introductionmentioning
confidence: 99%
“…Recently, an increasing number of studies have demonstrated that USP9X is involved with cancer (5)(6)(7)(8)(9)(10)(11)(12)(13)(14). USP9X expression was found to be higher in lung, colon and breast cancer, when compared with normal tissues in vitro (5,10).…”
Section: Discussionmentioning
confidence: 99%
“…USP9X expression was found to be higher in lung, colon and breast cancer, when compared with normal tissues in vitro (5,10). Furthermore, in lung and colon cancers, decreased USP9X expression resulted in the promotion of cellular apoptosis in vivo (5), which indicated that USP9X expression may be a potential predictor of such cancers.…”
Section: Discussionmentioning
confidence: 99%
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