Dataset Information

Extensive Rewiring of the EGFR Network in Colorectal Cancer Cells Expressing Transforming Levels of KRASG13D

ABSTRACT: RAW files of full proteome profiling of SILAC labeled HCT 116 and HKE 3 cells

INSTRUMENT(S): Orbitrap Fusion

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Epithelial Cell

DISEASE(S): Colon Cancer

SUBMITTER: Mohamed Ali Jarboui

LAB HEAD: Mohamed ali Jarboui

PROVIDER: PXD016549 | Pride | 2019-12-03

REPOSITORIES: Pride

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Publications

Extensive rewiring of the EGFR network in colorectal cancer cells expressing transforming levels of KRAS<sup>G13D</sup>.

Kennedy Susan A SA Jarboui Mohamed-Ali MA Srihari Sriganesh S Raso Cinzia C Bryan Kenneth K Dernayka Layal L Charitou Theodosia T Bernal-Llinares Manuel M Herrera-Montavez Carlos C Krstic Aleksandar A Matallanas David D Kotlyar Max M Jurisica Igor I Curak Jasna J Wong Victoria V Stagljar Igor I LeBihan Thierry T Imrie Lisa L Pillai Priyanka P Lynn Miriam A MA Fasterius Erik E Al-Khalili Szigyarto Cristina C Breen James J Kiel Christina C Serrano Luis L Rauch Nora N Rukhlenko Oleksii O Kholodenko Boris N BN Iglesias-Martinez Luis F LF Ryan Colm J CJ Pilkington Ruth R Cammareri Patrizia P Sansom Owen O Shave Steven S Auer Manfred M Horn Nicola N Klose Franziska F Ueffing Marius M Boldt Karsten K Lynn David J DJ Kolch Walter W

Nature communications 20200124 1

Protein-protein-interaction networks (PPINs) organize fundamental biological processes, but how oncogenic mutations impact these interactions and their functions at a network-level scale is poorly understood. Here, we analyze how a common oncogenic KRAS mutation (KRAS<sup>G13D</sup>) affects PPIN structure and function of the Epidermal Growth Factor Receptor (EGFR) network in colorectal cancer (CRC) cells. Mapping >6000 PPIs shows that this network is extensively rewired in cells expressing tran ...[more]

PMID: 31980649

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Project description:Cilia assembly, maintenance and the localization of signal-transduction proteins necessitate a functioning intraflagellar transport (IFT). The IFT machinery moves cargo along a microtubule scaffold from the proximal to the distal end of the cilium. This anterograde transport is facilitated by a large multiprotein complex IFT-B, which consists of 16 proteins in total and recruits motor protein Kinesin-2 for active movement. TTC30A and TTC30B are integral components of this complex and were shown before to have redundant function in context of IFT. One paralogue could compensate the loss of the other, preventing the disruption of IFT-B and thus a severe ciliogenesis defect with no formation of the cilium. Affinity-based protein complex analysis of endogenously tagged cells, generated via CRISPR/Cas9 system as described before, revealed paralogue specific protein interactors proposing the involvement of TTC30A or TTC30B in other ciliary functions, particularly Sonic hedgehog signaling (Shh). Defects in this ciliary signaling pathway are often correlated to synpolydactyly, which intriguingly is also linked to a rare TTC30 variant. In this study we focus on the so far unknown interaction of TTC30A with protein kinase A catalytic subunit α PRKACA, which is a negative regulator of Shh pathway. For an in-depth analysis of this unique interaction and the influence on Shh, we used previously, via the CRISPR/Cas9 system, generated TTC30A or B single- and double-knockout hTERT-RPE1 cells as well as rescue cells harboring the TTC30 mutation. Our systematic approach revealed the paralogue specific influence of TTC30A KO and mutated TTC30A on the activity of PRKACA as well as the uptake of Smoothened into the cilium resulting in a downregulation of Sonic hedgehog signaling. Affinity-based protein complex analysis of wildtype versus mutated TTC30A or TTC30B uncovered differences in interaction pattern. These interactome alterations combined with Shh downregulation suggest a possible mechanism of how mutant TTC30A and respectively TTC30A KO are linked to synpolydactyly.

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	ALI1879-S01-A-REV-1.raw	Raw
	ALI1879-S02-A-FOR-2.raw	Raw
	ALI1879-S02-A-REV-2.raw	Raw
	ALI1879-S03-A-FOR-3.raw	Raw