Identification of FoxM1/Bub1b signaling pathway as a required component for growth and survival of rhabdomyosarcoma

Xiaolin Wan; Choh Yeung; Su Young Kim; Joseph G. Dolan; Vu N. Ngo; Sandra Burkett; Javed Khan; Louis M. Staudt; Lee J. Helman

doi:10.1158/0008-5472.CAN-12-1991

Identification of FoxM1/Bub1b signaling pathway as a required component for growth and survival of rhabdomyosarcoma

Xiaolin Wan, Choh Yeung, Su Young Kim, Joseph G. Dolan, Vu N. Ngo, Sandra Burkett, Javed Khan, Louis M. Staudt, Lee J. Helman

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

31 Scopus citations

Abstract

We identified Bub1b as an essential element for the growth and survival of rhabdomyosarcoma (RMS) cells using a bar-coded, tetracycline-inducible short hairpin RNA (shRNA) library screen. Knockdown of Bub1b resulted in suppression of tumor growth in vivo, including the regression of established tumors. The mechanism by which this occurs is via postmitotic endoreduplication checkpoint and mitotic catastrophe. Furthermore, using a chromatin immunoprecipitation assay, we found that Bub1b is a direct transcriptional target of Forkhead Box M1 (FoxM1). Suppression of FoxM1 either by shRNA or the inhibitor siomycin A resulted in reduction of Bub1b expression and inhibition of cell growth and survival. These results show the important role of the Bub1b/ FoxM1 pathway in RMS and provide potential therapeutic targets.

Original language	English (US)
Pages (from-to)	5889-5899
Number of pages	11
Journal	Cancer Research
Volume	72
Issue number	22
DOIs	https://doi.org/10.1158/0008-5472.CAN-12-1991
State	Published - Nov 15 2012
Externally published	Yes

ASJC Scopus subject areas

Oncology
Cancer Research

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10.1158/0008-5472.CAN-12-1991

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title = "Identification of FoxM1/Bub1b signaling pathway as a required component for growth and survival of rhabdomyosarcoma",

abstract = "We identified Bub1b as an essential element for the growth and survival of rhabdomyosarcoma (RMS) cells using a bar-coded, tetracycline-inducible short hairpin RNA (shRNA) library screen. Knockdown of Bub1b resulted in suppression of tumor growth in vivo, including the regression of established tumors. The mechanism by which this occurs is via postmitotic endoreduplication checkpoint and mitotic catastrophe. Furthermore, using a chromatin immunoprecipitation assay, we found that Bub1b is a direct transcriptional target of Forkhead Box M1 (FoxM1). Suppression of FoxM1 either by shRNA or the inhibitor siomycin A resulted in reduction of Bub1b expression and inhibition of cell growth and survival. These results show the important role of the Bub1b/ FoxM1 pathway in RMS and provide potential therapeutic targets.",

author = "Xiaolin Wan and Choh Yeung and Kim, {Su Young} and Dolan, {Joseph G.} and Ngo, {Vu N.} and Sandra Burkett and Javed Khan and Staudt, {Louis M.} and Helman, {Lee J.}",

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doi = "10.1158/0008-5472.CAN-12-1991",

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T1 - Identification of FoxM1/Bub1b signaling pathway as a required component for growth and survival of rhabdomyosarcoma

AU - Wan, Xiaolin

AU - Yeung, Choh

AU - Kim, Su Young

AU - Dolan, Joseph G.

AU - Ngo, Vu N.

AU - Burkett, Sandra

AU - Khan, Javed

AU - Staudt, Louis M.

AU - Helman, Lee J.

PY - 2012/11/15

Y1 - 2012/11/15

N2 - We identified Bub1b as an essential element for the growth and survival of rhabdomyosarcoma (RMS) cells using a bar-coded, tetracycline-inducible short hairpin RNA (shRNA) library screen. Knockdown of Bub1b resulted in suppression of tumor growth in vivo, including the regression of established tumors. The mechanism by which this occurs is via postmitotic endoreduplication checkpoint and mitotic catastrophe. Furthermore, using a chromatin immunoprecipitation assay, we found that Bub1b is a direct transcriptional target of Forkhead Box M1 (FoxM1). Suppression of FoxM1 either by shRNA or the inhibitor siomycin A resulted in reduction of Bub1b expression and inhibition of cell growth and survival. These results show the important role of the Bub1b/ FoxM1 pathway in RMS and provide potential therapeutic targets.

AB - We identified Bub1b as an essential element for the growth and survival of rhabdomyosarcoma (RMS) cells using a bar-coded, tetracycline-inducible short hairpin RNA (shRNA) library screen. Knockdown of Bub1b resulted in suppression of tumor growth in vivo, including the regression of established tumors. The mechanism by which this occurs is via postmitotic endoreduplication checkpoint and mitotic catastrophe. Furthermore, using a chromatin immunoprecipitation assay, we found that Bub1b is a direct transcriptional target of Forkhead Box M1 (FoxM1). Suppression of FoxM1 either by shRNA or the inhibitor siomycin A resulted in reduction of Bub1b expression and inhibition of cell growth and survival. These results show the important role of the Bub1b/ FoxM1 pathway in RMS and provide potential therapeutic targets.

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Identification of FoxM1/Bub1b signaling pathway as a required component for growth and survival of rhabdomyosarcoma

Abstract

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