A protein network map of head and neck cancer reveals PIK3CA mutant drug sensitivity

Danielle L. Swaney; Dana J. Ramms; Zhiyong Wang; Jisoo Park; Yusuke Goto; Margaret Soucheray; Neil Bhola; Kyumin Kim; Fan Zheng; Yan Zeng; Michael McGregor; Kari A. Herrington; Rachel O'Keefe; Nan Jin; Nathan K. VanLandingham; Helene Foussard; John Von Dollen; Mehdi Bouhaddou; David Jimenez-Morales; Kirsten Obernier; Jason F. Kreisberg; Minkyu Kim; Daniel E. Johnson; Natalia Jura; Jennifer R. Grandis; J. Silvio Gutkind; Trey Ideker; Nevan J. Krogan

doi:10.1126/science.abf2911

A protein network map of head and neck cancer reveals PIK3CA mutant drug sensitivity

Danielle L. Swaney, Dana J. Ramms, Zhiyong Wang, Jisoo Park, Yusuke Goto, Margaret Soucheray, Neil Bhola, Kyumin Kim, Fan Zheng, Yan Zeng, Michael McGregor, Kari A. Herrington, Rachel O'Keefe, Nan Jin, Nathan K. VanLandingham, Helene Foussard, John Von Dollen, Mehdi Bouhaddou, David Jimenez-Morales, Kirsten ObernierJason F. Kreisberg, Minkyu Kim, Daniel E. Johnson, Natalia Jura, Jennifer R. Grandis, J. Silvio Gutkind, Trey Ideker, Nevan J. Krogan

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Abstract

We outline a framework for elucidating tumor genetic complexity through multidimensional proteinprotein interaction maps and apply it to enhancing our understanding of head and neck squamous cell carcinoma. This network uncovers 771 interactions from cancer and noncancerous cell states, including WT and mutant protein isoforms. Prioritization of cancer-enriched interactions reveals a previously unidentified association of the fibroblast growth factor receptor tyrosine kinase 3 with Daple, a guaninenucleotide exchange factor, resulting in activation of Gai- and p21-activated protein kinase 1/2 to promote cancer cell migration. Additionally, we observe mutation-enriched interactions between the human epidermal growth factor receptor 3 (HER3) receptor tyrosine kinase and PIK3CA (the alpha catalytic subunit of phosphatidylinositol 3-kinase) that can inform the response to HER3 inhibition in vivo. We anticipate that the application of this framework will be valuable for translating genetic alterations into a molecular and clinical understanding of the underlying biology of many disease areas.

Original language	English (US)
Article number	abf2911
Journal	Science
Volume	374
Issue number	6563
DOIs	https://doi.org/10.1126/science.abf2911
State	Published - Oct 1 2021
Externally published	Yes

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Swaney, D. L., Ramms, D. J., Wang, Z., Park, J., Goto, Y., Soucheray, M., Bhola, N., Kim, K., Zheng, F., Zeng, Y., McGregor, M., Herrington, K. A., O'Keefe, R., Jin, N., VanLandingham, N. K., Foussard, H., Von Dollen, J., Bouhaddou, M., Jimenez-Morales, D., ... Krogan, N. J. (2021). A protein network map of head and neck cancer reveals PIK3CA mutant drug sensitivity. Science, 374(6563), Article abf2911. https://doi.org/10.1126/science.abf2911

Swaney, DL, Ramms, DJ, Wang, Z, Park, J, Goto, Y, Soucheray, M, Bhola, N, Kim, K, Zheng, F, Zeng, Y, McGregor, M, Herrington, KA, O'Keefe, R, Jin, N, VanLandingham, NK, Foussard, H, Von Dollen, J, Bouhaddou, M, Jimenez-Morales, D, Obernier, K, Kreisberg, JF, Kim, M, Johnson, DE, Jura, N, Grandis, JR, Gutkind, JS, Ideker, T & Krogan, NJ 2021, 'A protein network map of head and neck cancer reveals PIK3CA mutant drug sensitivity', Science, vol. 374, no. 6563, abf2911. https://doi.org/10.1126/science.abf2911

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title = "A protein network map of head and neck cancer reveals PIK3CA mutant drug sensitivity",

abstract = "We outline a framework for elucidating tumor genetic complexity through multidimensional proteinprotein interaction maps and apply it to enhancing our understanding of head and neck squamous cell carcinoma. This network uncovers 771 interactions from cancer and noncancerous cell states, including WT and mutant protein isoforms. Prioritization of cancer-enriched interactions reveals a previously unidentified association of the fibroblast growth factor receptor tyrosine kinase 3 with Daple, a guaninenucleotide exchange factor, resulting in activation of Gai- and p21-activated protein kinase 1/2 to promote cancer cell migration. Additionally, we observe mutation-enriched interactions between the human epidermal growth factor receptor 3 (HER3) receptor tyrosine kinase and PIK3CA (the alpha catalytic subunit of phosphatidylinositol 3-kinase) that can inform the response to HER3 inhibition in vivo. We anticipate that the application of this framework will be valuable for translating genetic alterations into a molecular and clinical understanding of the underlying biology of many disease areas.",

author = "Swaney, {Danielle L.} and Ramms, {Dana J.} and Zhiyong Wang and Jisoo Park and Yusuke Goto and Margaret Soucheray and Neil Bhola and Kyumin Kim and Fan Zheng and Yan Zeng and Michael McGregor and Herrington, {Kari A.} and Rachel O'Keefe and Nan Jin and VanLandingham, {Nathan K.} and Helene Foussard and {Von Dollen}, John and Mehdi Bouhaddou and David Jimenez-Morales and Kirsten Obernier and Kreisberg, {Jason F.} and Minkyu Kim and Johnson, {Daniel E.} and Natalia Jura and Grandis, {Jennifer R.} and Gutkind, {J. Silvio} and Trey Ideker and Krogan, {Nevan J.}",

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AU - Swaney, Danielle L.

AU - Ramms, Dana J.

AU - Wang, Zhiyong

AU - Park, Jisoo

AU - Goto, Yusuke

AU - Soucheray, Margaret

AU - Bhola, Neil

AU - Kim, Kyumin

AU - Zheng, Fan

AU - Zeng, Yan

AU - McGregor, Michael

AU - Herrington, Kari A.

AU - O'Keefe, Rachel

AU - Jin, Nan

AU - VanLandingham, Nathan K.

AU - Foussard, Helene

AU - Von Dollen, John

AU - Bouhaddou, Mehdi

AU - Jimenez-Morales, David

AU - Obernier, Kirsten

AU - Kreisberg, Jason F.

AU - Kim, Minkyu

AU - Johnson, Daniel E.

AU - Jura, Natalia

AU - Grandis, Jennifer R.

AU - Gutkind, J. Silvio

AU - Ideker, Trey

AU - Krogan, Nevan J.

PY - 2021/10/1

Y1 - 2021/10/1

N2 - We outline a framework for elucidating tumor genetic complexity through multidimensional proteinprotein interaction maps and apply it to enhancing our understanding of head and neck squamous cell carcinoma. This network uncovers 771 interactions from cancer and noncancerous cell states, including WT and mutant protein isoforms. Prioritization of cancer-enriched interactions reveals a previously unidentified association of the fibroblast growth factor receptor tyrosine kinase 3 with Daple, a guaninenucleotide exchange factor, resulting in activation of Gai- and p21-activated protein kinase 1/2 to promote cancer cell migration. Additionally, we observe mutation-enriched interactions between the human epidermal growth factor receptor 3 (HER3) receptor tyrosine kinase and PIK3CA (the alpha catalytic subunit of phosphatidylinositol 3-kinase) that can inform the response to HER3 inhibition in vivo. We anticipate that the application of this framework will be valuable for translating genetic alterations into a molecular and clinical understanding of the underlying biology of many disease areas.

AB - We outline a framework for elucidating tumor genetic complexity through multidimensional proteinprotein interaction maps and apply it to enhancing our understanding of head and neck squamous cell carcinoma. This network uncovers 771 interactions from cancer and noncancerous cell states, including WT and mutant protein isoforms. Prioritization of cancer-enriched interactions reveals a previously unidentified association of the fibroblast growth factor receptor tyrosine kinase 3 with Daple, a guaninenucleotide exchange factor, resulting in activation of Gai- and p21-activated protein kinase 1/2 to promote cancer cell migration. Additionally, we observe mutation-enriched interactions between the human epidermal growth factor receptor 3 (HER3) receptor tyrosine kinase and PIK3CA (the alpha catalytic subunit of phosphatidylinositol 3-kinase) that can inform the response to HER3 inhibition in vivo. We anticipate that the application of this framework will be valuable for translating genetic alterations into a molecular and clinical understanding of the underlying biology of many disease areas.

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A protein network map of head and neck cancer reveals PIK3CA mutant drug sensitivity

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