American Association for Cancer Research
10780432ccr151673-sup-152630_2_supp_3444889_s5hscp.docx (12.56 kB)

Supplementary Figures 3-5 Legends from Tyrosine Kinase Signaling in Clear Cell and Papillary Renal Cell Carcinoma Revealed by Mass Spectrometry–Based Phosphotyrosine Proteomics

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journal contribution
posted on 2023-03-31, 18:22 authored by Scott M. Haake, Jiannong Li, Yun Bai, Fumi Kinose, Bin Fang, Eric A. Welsh, Roy Zent, Jasreman Dhillon, Julio M. Pow-Sang, Y. Ann Chen, John M. Koomen, W. Kimryn Rathmell, Mayer Fishman, Eric B. Haura

Supplementary Figures 3-5 Legends


Conquer Cancer Foundation Young Investigator Award

Moffitt Cancer Center Department of Genitourinary Oncology

NCI-designated Comprehensive Cancer Center



Purpose: Targeted therapies in renal cell carcinoma (RCC) are limited by acquired resistance. Novel therapeutic targets are needed to combat resistance and, ideally, target the unique biology of RCC subtypes.Experimental Design: Tyrosine kinases provide critical oncogenic signaling and their inhibition has significantly impacted cancer care. To describe a landscape of tyrosine kinase activity in RCC that could inform novel therapeutic strategies, we performed a mass spectrometry–based system-wide survey of tyrosine phosphorylation in 10 RCC cell lines as well as 15 clear cell and 15 papillary RCC human tumors. To prioritize identified tyrosine kinases for further analysis, a 63 tyrosine kinase inhibitor (TKI) drug screen was performed.Results: Among the cell lines, 28 unique tyrosine phosphosites were identified across 19 kinases and phosphatases including EGFR, MET, JAK2, and FAK in nearly all samples. Multiple FAK TKIs decreased cell viability by at least 50% and inhibited RCC cell line adhesion, invasion, and proliferation. Among the tumors, 49 unique tyrosine phosphosites were identified across 44 kinases and phosphatases. FAK pY576/7 was found in all tumors and many cell lines, whereas DDR1 pY792/6 was preferentially enriched in the papillary RCC tumors. Both tyrosine kinases are capable of transmitting signals from the extracellular matrix and emerged as novel RCC therapeutic targets.Conclusions: Tyrosine kinase profiling informs novel therapeutic strategies in RCC and highlights the unique biology among kidney cancer subtypes. Clin Cancer Res; 22(22); 5605–16. ©2016 AACR.