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

ABSTRACT: Despite extensive DNA sequencing of patient tumors, it remains challenging to translate the immense landscape of heterogeneous genetic alterations into function and clinical outcomes due to a limited understanding of cancer specific molecular network architectures. To bridge this gap, we have used affinity purification-mass spectrometry to generate protein interaction networks for 31 proteins with significant alterations in head and neck squamous cell carcinoma. This network includes 771 interactions covering both cancer and non-tumorigenic cell states, as well as wild-type and mutant proteins. Differential analysis across these dimensions reveals a strong interaction between PIK3CA and ERBB3 (HER3), dependent upon mutations in PIK3CA. We show that this interaction correlates with ERBB3 activity in vitro and can be targeted in vivo using a clinical ERBB3 inhibitor, CDX3379, to prohibit growth of tumors with common PIK3CA mutations. This study provides a roadmap for elucidating genetic complexity through multidimensional maps of cancer cell biology.

INSTRUMENT(S): Q Exactive Plus, LTQ Orbitrap Elite

ORGANISM(S): Homo Sapiens (human)

DISEASE(S): Head And Neck Squamous Cell Carcinoma

SUBMITTER: Danielle Swaney

LAB HEAD: Danielle Swaney / Nevan Krogan

PROVIDER: PXD019469 | Pride | 2021-10-07

REPOSITORIES: Pride

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			Action	DRS
	CAL33_MQ.zip	Other
	HET1A_MQ.zip	Other
	MaxQuant_1.6.2.10.zip	Other
	QE20150703-80.raw	Raw
	QE20150703-82.raw	Raw

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