Glioma pathogenesis-related protein 1 induces prostate cancer cell death through Hsc70-mediated suppression of AURKA and TPX2

Likun Li; Guang Yang; Chengzhen Ren; Ryuta Tanimoto; Takahiro Hirayama; Jianxiang Wang; David Hawke; Soo Mi Kim; Ju Seog Lee; Alexei A. Goltsov; Sanghee Park; Michael M. Ittmann; Patricia Troncoso; Timothy C. Thompson

doi:10.1016/j.molonc.2012.12.005

Glioma pathogenesis-related protein 1 induces prostate cancer cell death through Hsc70-mediated suppression of AURKA and TPX2

Likun Li, Guang Yang, Chengzhen Ren, Ryuta Tanimoto, Takahiro Hirayama, Jianxiang Wang, David Hawke, Soo Mi Kim, Ju Seog Lee, Alexei A. Goltsov, Sanghee Park, Michael M. Ittmann, Patricia Troncoso, Timothy C. Thompson

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30 Scopus citations

Abstract

In this study we report that expression of glioma pathogenesis-related protein 1 (GLIPR1) regulated numerous apoptotic, cell cycle, and spindle/centrosome assembly-related genes, including AURKA and TPX2, and induced apoptosis and/or mitotic catastrophe (MC) in prostate cancer (PCa) cells, including p53-mutated/deleted, androgen-insensitive metastatic PCa cells. Mechanistically, GLIPR1 interacts with heat shock cognate protein 70 (Hsc70); this interaction is associated with SP1 and c-Myb destabilization and suppression of SP1- and c-Myb-mediated AURKA and TPX2 transcription. Inhibition of AURKA and TPX2 using siRNA mimicked enforced GLIPR1 expression in the induction of apoptosis and MC. Recombinant GLIPR1-ΔTM protein inhibited AURKA and TPX2 expression, induced apoptosis and MC, and suppressed orthotopic xenograft tumor growth. Our results define a novel GLIPR1-regulated signaling pathway that controls apoptosis and/or mitotic catastrophe in PCa cells and establishes the potential of this pathway for targeted therapies.

Original language	English (US)
Pages (from-to)	484-496
Number of pages	13
Journal	Molecular oncology
Volume	7
Issue number	3
DOIs	https://doi.org/10.1016/j.molonc.2012.12.005
State	Published - Jun 2013

Keywords

AURKA
C-Myb
Glioma pathogenesis-related protein 1 (GLIPR1)
Hsc70
Prostate cancer
TPX2

ASJC Scopus subject areas

Molecular Medicine
Genetics
Oncology
Cancer Research

MD Anderson CCSG core facilities

Advanced Technology Genomics Core
Research Animal Support Facility
Cytogenetics and Cell Authentication Core
Proteomics Facility

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10.1016/j.molonc.2012.12.005

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Li, L., Yang, G., Ren, C., Tanimoto, R., Hirayama, T., Wang, J., Hawke, D., Kim, S. M., Lee, J. S., Goltsov, A. A., Park, S., Ittmann, M. M., Troncoso, P., & Thompson, T. C. (2013). Glioma pathogenesis-related protein 1 induces prostate cancer cell death through Hsc70-mediated suppression of AURKA and TPX2. Molecular oncology, 7(3), 484-496. https://doi.org/10.1016/j.molonc.2012.12.005

Li, L, Yang, G, Ren, C, Tanimoto, R, Hirayama, T, Wang, J, Hawke, D, Kim, SM, Lee, JS , Goltsov, AA, Park, S, Ittmann, MM, Troncoso, P & Thompson, TC 2013, 'Glioma pathogenesis-related protein 1 induces prostate cancer cell death through Hsc70-mediated suppression of AURKA and TPX2', Molecular oncology, vol. 7, no. 3, pp. 484-496. https://doi.org/10.1016/j.molonc.2012.12.005

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title = "Glioma pathogenesis-related protein 1 induces prostate cancer cell death through Hsc70-mediated suppression of AURKA and TPX2",

abstract = "In this study we report that expression of glioma pathogenesis-related protein 1 (GLIPR1) regulated numerous apoptotic, cell cycle, and spindle/centrosome assembly-related genes, including AURKA and TPX2, and induced apoptosis and/or mitotic catastrophe (MC) in prostate cancer (PCa) cells, including p53-mutated/deleted, androgen-insensitive metastatic PCa cells. Mechanistically, GLIPR1 interacts with heat shock cognate protein 70 (Hsc70); this interaction is associated with SP1 and c-Myb destabilization and suppression of SP1- and c-Myb-mediated AURKA and TPX2 transcription. Inhibition of AURKA and TPX2 using siRNA mimicked enforced GLIPR1 expression in the induction of apoptosis and MC. Recombinant GLIPR1-ΔTM protein inhibited AURKA and TPX2 expression, induced apoptosis and MC, and suppressed orthotopic xenograft tumor growth. Our results define a novel GLIPR1-regulated signaling pathway that controls apoptosis and/or mitotic catastrophe in PCa cells and establishes the potential of this pathway for targeted therapies.",

keywords = "AURKA, C-Myb, Glioma pathogenesis-related protein 1 (GLIPR1), Hsc70, Prostate cancer, TPX2",

author = "Likun Li and Guang Yang and Chengzhen Ren and Ryuta Tanimoto and Takahiro Hirayama and Jianxiang Wang and David Hawke and Kim, {Soo Mi} and Lee, {Ju Seog} and Goltsov, {Alexei A.} and Sanghee Park and Ittmann, {Michael M.} and Patricia Troncoso and Thompson, {Timothy C.}",

note = "Funding Information: We thank Karen F. Phillips, ELS(D), for editing the manuscript. This work was supported in part by National Cancer Institute grants R0150588 (to T.C.T.) and P50140388 , the Prostate Cancer Specialized Program of Research Excellence at The University of Texas MD Anderson Cancer Center; in part by the National Institutes of Health through MD Anderson's Cancer Center Support Grant, CA016672 ; and in part by Tony's Prostate Cancer Research foundation. ",

year = "2013",

month = jun,

doi = "10.1016/j.molonc.2012.12.005",

language = "English (US)",

volume = "7",

pages = "484--496",

journal = "Molecular oncology",

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T1 - Glioma pathogenesis-related protein 1 induces prostate cancer cell death through Hsc70-mediated suppression of AURKA and TPX2

AU - Li, Likun

AU - Yang, Guang

AU - Ren, Chengzhen

AU - Tanimoto, Ryuta

AU - Hirayama, Takahiro

AU - Wang, Jianxiang

AU - Hawke, David

AU - Kim, Soo Mi

AU - Lee, Ju Seog

AU - Goltsov, Alexei A.

AU - Park, Sanghee

AU - Ittmann, Michael M.

AU - Troncoso, Patricia

AU - Thompson, Timothy C.

N1 - Funding Information: We thank Karen F. Phillips, ELS(D), for editing the manuscript. This work was supported in part by National Cancer Institute grants R0150588 (to T.C.T.) and P50140388 , the Prostate Cancer Specialized Program of Research Excellence at The University of Texas MD Anderson Cancer Center; in part by the National Institutes of Health through MD Anderson's Cancer Center Support Grant, CA016672 ; and in part by Tony's Prostate Cancer Research foundation.

PY - 2013/6

Y1 - 2013/6

N2 - In this study we report that expression of glioma pathogenesis-related protein 1 (GLIPR1) regulated numerous apoptotic, cell cycle, and spindle/centrosome assembly-related genes, including AURKA and TPX2, and induced apoptosis and/or mitotic catastrophe (MC) in prostate cancer (PCa) cells, including p53-mutated/deleted, androgen-insensitive metastatic PCa cells. Mechanistically, GLIPR1 interacts with heat shock cognate protein 70 (Hsc70); this interaction is associated with SP1 and c-Myb destabilization and suppression of SP1- and c-Myb-mediated AURKA and TPX2 transcription. Inhibition of AURKA and TPX2 using siRNA mimicked enforced GLIPR1 expression in the induction of apoptosis and MC. Recombinant GLIPR1-ΔTM protein inhibited AURKA and TPX2 expression, induced apoptosis and MC, and suppressed orthotopic xenograft tumor growth. Our results define a novel GLIPR1-regulated signaling pathway that controls apoptosis and/or mitotic catastrophe in PCa cells and establishes the potential of this pathway for targeted therapies.

AB - In this study we report that expression of glioma pathogenesis-related protein 1 (GLIPR1) regulated numerous apoptotic, cell cycle, and spindle/centrosome assembly-related genes, including AURKA and TPX2, and induced apoptosis and/or mitotic catastrophe (MC) in prostate cancer (PCa) cells, including p53-mutated/deleted, androgen-insensitive metastatic PCa cells. Mechanistically, GLIPR1 interacts with heat shock cognate protein 70 (Hsc70); this interaction is associated with SP1 and c-Myb destabilization and suppression of SP1- and c-Myb-mediated AURKA and TPX2 transcription. Inhibition of AURKA and TPX2 using siRNA mimicked enforced GLIPR1 expression in the induction of apoptosis and MC. Recombinant GLIPR1-ΔTM protein inhibited AURKA and TPX2 expression, induced apoptosis and MC, and suppressed orthotopic xenograft tumor growth. Our results define a novel GLIPR1-regulated signaling pathway that controls apoptosis and/or mitotic catastrophe in PCa cells and establishes the potential of this pathway for targeted therapies.

KW - AURKA

KW - C-Myb

KW - Glioma pathogenesis-related protein 1 (GLIPR1)

KW - Hsc70

KW - Prostate cancer

KW - TPX2

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ER -

Glioma pathogenesis-related protein 1 induces prostate cancer cell death through Hsc70-mediated suppression of AURKA and TPX2

Abstract

Keywords

ASJC Scopus subject areas

MD Anderson CCSG core facilities

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