Genetic disruption of USP9X sensitizes colorectal cancer cells to 5-fluorouracil

Dennis R. Harris; Alexandra Mims; Fred Bunz

doi:10.4161/cbt.21792

Genetic disruption of USP9X sensitizes colorectal cancer cells to 5-fluorouracil

Dennis R. Harris, Alexandra Mims, Fred Bunz

School of Medicine

Research output: Contribution to journal › Article › peer-review

29 Scopus citations

Abstract

The X-linked deubiquitinase USP 9X affects the stability and activity of numerous regulatory proteins that influence cell survival. Recent studies suggest that decreased USP 9X expression can confer a selective advantage onto developing cancer cells and thereby promotes disease progression. To examine the effect of USP 9X on the cellular responses to anticancer therapies, we derived cancer cell lines in which the USP9X locus was disrupted by homologous recombination. The resulting USP 9X-deficient cancer cells exhibited increased activation of apoptotic pathways and markedly decreased clonogenic survival in response to 5-fluorouracil, a chemotherapeutic drug that is widely used for treatment of gastrointestinal malignancies. These unexpected results suggest that cancers with low USP9X expression might be specifically sensitized to some conventional therapeutic agents.

Original language	English (US)
Pages (from-to)	1319-1324
Number of pages	6
Journal	Cancer Biology and Therapy
Volume	13
Issue number	13
DOIs	https://doi.org/10.4161/cbt.21792
State	Published - Nov 2012

Keywords

5-fluorouracil
Apoptosis
Chemotherapy
Gene targeting
P53
Resistance
USP9X

ASJC Scopus subject areas

Molecular Medicine
Oncology
Pharmacology
Cancer Research

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title = "Genetic disruption of USP9X sensitizes colorectal cancer cells to 5-fluorouracil",

abstract = "The X-linked deubiquitinase USP 9X affects the stability and activity of numerous regulatory proteins that influence cell survival. Recent studies suggest that decreased USP 9X expression can confer a selective advantage onto developing cancer cells and thereby promotes disease progression. To examine the effect of USP 9X on the cellular responses to anticancer therapies, we derived cancer cell lines in which the USP9X locus was disrupted by homologous recombination. The resulting USP 9X-deficient cancer cells exhibited increased activation of apoptotic pathways and markedly decreased clonogenic survival in response to 5-fluorouracil, a chemotherapeutic drug that is widely used for treatment of gastrointestinal malignancies. These unexpected results suggest that cancers with low USP9X expression might be specifically sensitized to some conventional therapeutic agents.",

keywords = "5-fluorouracil, Apoptosis, Chemotherapy, Gene targeting, P53, Resistance, USP9X",

author = "Harris, {Dennis R.} and Alexandra Mims and Fred Bunz",

note = "Funding Information: This study was supported by funds from the Johns Hopkins SPORE in gastrointestinal cancer (P50CA062924) and a grant from the National Cancer Institute to F.B. (R01157535). D.R.H. was supported by a training grant from the National Cancer Institute (T32CA121937).",

year = "2012",

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doi = "10.4161/cbt.21792",

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AU - Mims, Alexandra

AU - Bunz, Fred

N1 - Funding Information: This study was supported by funds from the Johns Hopkins SPORE in gastrointestinal cancer (P50CA062924) and a grant from the National Cancer Institute to F.B. (R01157535). D.R.H. was supported by a training grant from the National Cancer Institute (T32CA121937).

PY - 2012/11

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N2 - The X-linked deubiquitinase USP 9X affects the stability and activity of numerous regulatory proteins that influence cell survival. Recent studies suggest that decreased USP 9X expression can confer a selective advantage onto developing cancer cells and thereby promotes disease progression. To examine the effect of USP 9X on the cellular responses to anticancer therapies, we derived cancer cell lines in which the USP9X locus was disrupted by homologous recombination. The resulting USP 9X-deficient cancer cells exhibited increased activation of apoptotic pathways and markedly decreased clonogenic survival in response to 5-fluorouracil, a chemotherapeutic drug that is widely used for treatment of gastrointestinal malignancies. These unexpected results suggest that cancers with low USP9X expression might be specifically sensitized to some conventional therapeutic agents.

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KW - 5-fluorouracil

KW - Apoptosis

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KW - Gene targeting

KW - P53

KW - Resistance

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Genetic disruption of USP9X sensitizes colorectal cancer cells to 5-fluorouracil

Abstract

Keywords

ASJC Scopus subject areas

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