The ZNF304-integrin axis protects against anoikis in cancer

Burcu Aslan; Paloma Monroig; Ming Chuan Hsu; Guillermo Armaiz Pena; Cristian Rodriguez-Aguayo; Vianey Gonzalez-Villasana; Rajesha Rupaimoole; Archana Sidalaghatta Nagaraja; Selanere Mangala; Hee Dong Han; Erkan Yuca; Sherry Y. Wu; Cristina Ivan; Tyler J. Moss; Prahlad T. Ram; Huamin Wang; Alexandra Gol-Chambers; Ozgur Ozkayar; Pinar Kanlikilicer; Enrique Fuentes-Mattei; Nermin Kahraman; Sunila Pradeep; Bulent Ozpolat; Susan Tucker; Mien Chie Hung; Keith Baggerly; Geoffrey Bartholomeusz; George Calin; Anil K. Sood; Gabriel Lopez-Berestein

doi:10.1038/ncomms8351

The ZNF304-integrin axis protects against anoikis in cancer

Burcu Aslan, Paloma Monroig, Ming Chuan Hsu, Guillermo Armaiz Pena, Cristian Rodriguez-Aguayo, Vianey Gonzalez-Villasana, Rajesha Rupaimoole, Archana Sidalaghatta Nagaraja, Selanere Mangala, Hee Dong Han, Erkan Yuca, Sherry Y. Wu, Cristina Ivan, Tyler J. Moss, Prahlad T. Ram, Huamin Wang, Alexandra Gol-Chambers, Ozgur Ozkayar, Pinar Kanlikilicer, Enrique Fuentes-MatteiNermin Kahraman, Sunila Pradeep, Bulent Ozpolat, Susan Tucker, Mien Chie Hung, Keith Baggerly, Geoffrey Bartholomeusz, George Calin, Anil K. Sood, Gabriel Lopez-Berestein

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

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Abstract

Ovarian cancer (OC) is a highly metastatic disease, but no effective strategies to target this process are currently available. Here, an integrative computational analysis of the Cancer Genome Atlas OC data set and experimental validation identifies a zinc finger transcription factor ZNF304 associated with OC metastasis. High tumoral ZNF304 expression is associated with poor overall survival in OC patients. Through reverse phase protein array analysis, we demonstrate that ZNF304 promotes multiple proto-oncogenic pathways important for cell survival, migration and invasion. ZNF304 transcriptionally regulates β1 integrin, which subsequently regulates Src/focal adhesion kinase and paxillin and prevents anoikis. In vivo delivery of ZNF304 siRNA by a dual assembly nanoparticle leads to sustained gene silencing for 14 days, increased anoikis and reduced tumour growth in orthotopic mouse models of OC. Taken together, ZNF304 is a transcriptional regulator of β1 integrin, promotes cancer cell survival and protects against anoikis in OC.

Original language	English (US)
Article number	7351
Journal	Nature communications
Volume	6
DOIs	https://doi.org/10.1038/ncomms8351
State	Published - Jun 17 2015

ASJC Scopus subject areas

General Chemistry
General Biochemistry, Genetics and Molecular Biology
General Physics and Astronomy

MD Anderson CCSG core facilities

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Flow Cytometry and Cellular Imaging Facility
Functional Proteomics Reverse Phase Protein Array Core
Research Animal Support Facility

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10.1038/ncomms8351

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Aslan, B., Monroig, P., Hsu, M. C., Pena, G. A., Rodriguez-Aguayo, C., Gonzalez-Villasana, V., Rupaimoole, R., Nagaraja, A. S., Mangala, S., Han, H. D., Yuca, E., Wu, S. Y., Ivan, C., Moss, T. J., Ram, P. T., Wang, H., Gol-Chambers, A., Ozkayar, O., Kanlikilicer, P., ... Lopez-Berestein, G. (2015). The ZNF304-integrin axis protects against anoikis in cancer. Nature communications, 6, Article 7351. https://doi.org/10.1038/ncomms8351

Aslan, B, Monroig, P, Hsu, MC, Pena, GA, Rodriguez-Aguayo, C, Gonzalez-Villasana, V, Rupaimoole, R, Nagaraja, AS, Mangala, S, Han, HD, Yuca, E, Wu, SY, Ivan, C, Moss, TJ, Ram, PT, Wang, H, Gol-Chambers, A, Ozkayar, O, Kanlikilicer, P, Fuentes-Mattei, E, Kahraman, N, Pradeep, S, Ozpolat, B, Tucker, S, Hung, MC, Baggerly, K, Bartholomeusz, G, Calin, G , Sood, AK & Lopez-Berestein, G 2015, 'The ZNF304-integrin axis protects against anoikis in cancer', Nature communications, vol. 6, 7351. https://doi.org/10.1038/ncomms8351

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title = "The ZNF304-integrin axis protects against anoikis in cancer",

abstract = "Ovarian cancer (OC) is a highly metastatic disease, but no effective strategies to target this process are currently available. Here, an integrative computational analysis of the Cancer Genome Atlas OC data set and experimental validation identifies a zinc finger transcription factor ZNF304 associated with OC metastasis. High tumoral ZNF304 expression is associated with poor overall survival in OC patients. Through reverse phase protein array analysis, we demonstrate that ZNF304 promotes multiple proto-oncogenic pathways important for cell survival, migration and invasion. ZNF304 transcriptionally regulates β1 integrin, which subsequently regulates Src/focal adhesion kinase and paxillin and prevents anoikis. In vivo delivery of ZNF304 siRNA by a dual assembly nanoparticle leads to sustained gene silencing for 14 days, increased anoikis and reduced tumour growth in orthotopic mouse models of OC. Taken together, ZNF304 is a transcriptional regulator of β1 integrin, promotes cancer cell survival and protects against anoikis in OC.",

author = "Burcu Aslan and Paloma Monroig and Hsu, {Ming Chuan} and Pena, {Guillermo Armaiz} and Cristian Rodriguez-Aguayo and Vianey Gonzalez-Villasana and Rajesha Rupaimoole and Nagaraja, {Archana Sidalaghatta} and Selanere Mangala and Han, {Hee Dong} and Erkan Yuca and Wu, {Sherry Y.} and Cristina Ivan and Moss, {Tyler J.} and Ram, {Prahlad T.} and Huamin Wang and Alexandra Gol-Chambers and Ozgur Ozkayar and Pinar Kanlikilicer and Enrique Fuentes-Mattei and Nermin Kahraman and Sunila Pradeep and Bulent Ozpolat and Susan Tucker and Hung, {Mien Chie} and Keith Baggerly and Geoffrey Bartholomeusz and George Calin and Sood, {Anil K.} and Gabriel Lopez-Berestein",

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doi = "10.1038/ncomms8351",

language = "English (US)",

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AU - Aslan, Burcu

AU - Monroig, Paloma

AU - Hsu, Ming Chuan

AU - Pena, Guillermo Armaiz

AU - Rodriguez-Aguayo, Cristian

AU - Gonzalez-Villasana, Vianey

AU - Rupaimoole, Rajesha

AU - Nagaraja, Archana Sidalaghatta

AU - Mangala, Selanere

AU - Han, Hee Dong

AU - Yuca, Erkan

AU - Wu, Sherry Y.

AU - Ivan, Cristina

AU - Moss, Tyler J.

AU - Ram, Prahlad T.

AU - Wang, Huamin

AU - Gol-Chambers, Alexandra

AU - Ozkayar, Ozgur

AU - Kanlikilicer, Pinar

AU - Fuentes-Mattei, Enrique

AU - Kahraman, Nermin

AU - Pradeep, Sunila

AU - Ozpolat, Bulent

AU - Tucker, Susan

AU - Hung, Mien Chie

AU - Baggerly, Keith

AU - Bartholomeusz, Geoffrey

AU - Calin, George

AU - Sood, Anil K.

AU - Lopez-Berestein, Gabriel

PY - 2015/6/17

Y1 - 2015/6/17

N2 - Ovarian cancer (OC) is a highly metastatic disease, but no effective strategies to target this process are currently available. Here, an integrative computational analysis of the Cancer Genome Atlas OC data set and experimental validation identifies a zinc finger transcription factor ZNF304 associated with OC metastasis. High tumoral ZNF304 expression is associated with poor overall survival in OC patients. Through reverse phase protein array analysis, we demonstrate that ZNF304 promotes multiple proto-oncogenic pathways important for cell survival, migration and invasion. ZNF304 transcriptionally regulates β1 integrin, which subsequently regulates Src/focal adhesion kinase and paxillin and prevents anoikis. In vivo delivery of ZNF304 siRNA by a dual assembly nanoparticle leads to sustained gene silencing for 14 days, increased anoikis and reduced tumour growth in orthotopic mouse models of OC. Taken together, ZNF304 is a transcriptional regulator of β1 integrin, promotes cancer cell survival and protects against anoikis in OC.

AB - Ovarian cancer (OC) is a highly metastatic disease, but no effective strategies to target this process are currently available. Here, an integrative computational analysis of the Cancer Genome Atlas OC data set and experimental validation identifies a zinc finger transcription factor ZNF304 associated with OC metastasis. High tumoral ZNF304 expression is associated with poor overall survival in OC patients. Through reverse phase protein array analysis, we demonstrate that ZNF304 promotes multiple proto-oncogenic pathways important for cell survival, migration and invasion. ZNF304 transcriptionally regulates β1 integrin, which subsequently regulates Src/focal adhesion kinase and paxillin and prevents anoikis. In vivo delivery of ZNF304 siRNA by a dual assembly nanoparticle leads to sustained gene silencing for 14 days, increased anoikis and reduced tumour growth in orthotopic mouse models of OC. Taken together, ZNF304 is a transcriptional regulator of β1 integrin, promotes cancer cell survival and protects against anoikis in OC.

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The ZNF304-integrin axis protects against anoikis in cancer

Abstract

ASJC Scopus subject areas

MD Anderson CCSG core facilities

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