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1. Figure S3 from Oncogenic KRAS Recruits an Expansive Transcriptional Network through Mutant p53 to Drive Pancreatic Cancer Metastasis

Author

Guillermina Lozano, Jason B. Fleming, Amanda R. Wasylishen, Michelle C. Barton, Bin Liu, Anirban Maitra, Timothy P. Heffernan, Christopher A. Bristow, Florencia McAllister, Eugene J. Koay, Shunbin Xiong, Joy M. McDaniel, Ya'an Kang, Jithesh J. Augustine, Christian Siangco, Tara G. Hughes, Kendra L. Allton, Bingbing Dai, Yun Zhang, Jenying Deng, Xinqun Li, and Michael P. Kim

Abstract

Supplementary Figure 3

Published
2023
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2. Figure S1 from Oncogenic KRAS Recruits an Expansive Transcriptional Network through Mutant p53 to Drive Pancreatic Cancer Metastasis

Author

Guillermina Lozano, Jason B. Fleming, Amanda R. Wasylishen, Michelle C. Barton, Bin Liu, Anirban Maitra, Timothy P. Heffernan, Christopher A. Bristow, Florencia McAllister, Eugene J. Koay, Shunbin Xiong, Joy M. McDaniel, Ya'an Kang, Jithesh J. Augustine, Christian Siangco, Tara G. Hughes, Kendra L. Allton, Bingbing Dai, Yun Zhang, Jenying Deng, Xinqun Li, and Michael P. Kim

Abstract

Supplementary Figure 1

Published
2023
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3. Mutant p53-associated genes from Oncogenic KRAS Recruits an Expansive Transcriptional Network through Mutant p53 to Drive Pancreatic Cancer Metastasis

Author

Guillermina Lozano, Jason B. Fleming, Amanda R. Wasylishen, Michelle C. Barton, Bin Liu, Anirban Maitra, Timothy P. Heffernan, Christopher A. Bristow, Florencia McAllister, Eugene J. Koay, Shunbin Xiong, Joy M. McDaniel, Ya'an Kang, Jithesh J. Augustine, Christian Siangco, Tara G. Hughes, Kendra L. Allton, Bingbing Dai, Yun Zhang, Jenying Deng, Xinqun Li, and Michael P. Kim

Abstract

Mutant p53-associated genes

Published
2023
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4. Figure S2 from Oncogenic KRAS Recruits an Expansive Transcriptional Network through Mutant p53 to Drive Pancreatic Cancer Metastasis

Author

Guillermina Lozano, Jason B. Fleming, Amanda R. Wasylishen, Michelle C. Barton, Bin Liu, Anirban Maitra, Timothy P. Heffernan, Christopher A. Bristow, Florencia McAllister, Eugene J. Koay, Shunbin Xiong, Joy M. McDaniel, Ya'an Kang, Jithesh J. Augustine, Christian Siangco, Tara G. Hughes, Kendra L. Allton, Bingbing Dai, Yun Zhang, Jenying Deng, Xinqun Li, and Michael P. Kim

Abstract

Supplementary Figure 2

Published
2023
Full Text
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5. Figure S5 from Oncogenic KRAS Recruits an Expansive Transcriptional Network through Mutant p53 to Drive Pancreatic Cancer Metastasis

Author

Guillermina Lozano, Jason B. Fleming, Amanda R. Wasylishen, Michelle C. Barton, Bin Liu, Anirban Maitra, Timothy P. Heffernan, Christopher A. Bristow, Florencia McAllister, Eugene J. Koay, Shunbin Xiong, Joy M. McDaniel, Ya'an Kang, Jithesh J. Augustine, Christian Siangco, Tara G. Hughes, Kendra L. Allton, Bingbing Dai, Yun Zhang, Jenying Deng, Xinqun Li, and Michael P. Kim

Abstract

Supplementary Figure 5

Published
2023
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7. Oncogenic

Author

Michael P, Kim, Xinqun, Li, Jenying, Deng, Yun, Zhang, Bingbing, Dai, Kendra L, Allton, Tara G, Hughes, Christian, Siangco, Jithesh J, Augustine, Ya'an, Kang, Joy M, McDaniel, Shunbin, Xiong, Eugene J, Koay, Florencia, McAllister, Christopher A, Bristow, Timothy P, Heffernan, Anirban, Maitra, Bin, Liu, Michelle C, Barton, Amanda R, Wasylishen, Jason B, Fleming, and Guillermina, Lozano

Subjects
endocrine system diseases, Mice, Nude, Genes, p53, digestive system diseases, Article, Mice, Inbred C57BL, Pancreatic Neoplasms, Proto-Oncogene Proteins p21(ras), Mice, Animals, Humans, Female, Gene Regulatory Networks, Neoplasm Metastasis, Carcinoma, Pancreatic Ductal
Abstract

Pancreatic ductal adenocarcinoma (PDAC) is almost uniformly fatal and characterized by early metastasis. Oncogenic KRAS mutations prevail in 95% of PDAC tumors and co-occur with genetic alterations in the TP53 tumor suppressor in nearly 70% of patients. Most TP53 alterations are missense mutations that exhibit gain-of-function phenotypes that include increased invasiveness and metastasis yet the extent of direct cooperation between KRAS effectors and mutant p53 remains largely undefined. We show that oncogenic KRAS effectors activate cyclic AMP responsive element binding protein 1 (CREB1) to allow physical interactions with mutant p53 that hyperactivate multiple pro-metastatic transcriptional networks. Specifically, mutant p53 and CREB1 upregulate the pro-metastatic, pioneer transcription factor, FOXA1, activating its transcriptional network while promoting WNT/β-catenin signaling, together driving PDAC metastasis. Pharmacologic CREB1 inhibition dramatically reduced FOXA1 and β-catenin expression and dampened PDAC metastasis, identifying a new therapeutic strategy to disrupt cooperation between oncogenic KRAS and mutant p53 to mitigate metastasis.

Published
2020

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