Quantitative phosphoproteomic analysis reveals system-wide signaling pathways regulated by site-specific phosphorylation on Keratin-8 in skin squamous cell carcinoma derived cell-line

ABSTRACT: The epithelial specific keratin pair, Keratin 8/18 (K8/18), has been reported to be aberrantly expressed in squamous cell carcinoma (SCC) which is also correlated with increased invasiveness and poor prognosis. A Majority of Keratin 8 (K8) functions are governed by its phosphorylation at Serine73 (head domain) and Serine431 (tail domain) residues. Although deregulation of K8 phosphorylation has been associated with progression of different carcinomas, its role in skin SCC and the underlying mechanism is obscured. To understand the molecular basis of K8 phosphorylation mediated regulation of skin SCC progression, we performed TMT-based quantitative phosphoproteomics by expressing K8 wild type, phosphodead and phosphomimetic mutants in K8 deficient A431 cells. Bioinformatic analysis of our phosphoproteomic data showed differential regulation of phosphoproteins associated with migratory, proliferative and invasive potential in these cells. Further validation of protein phosphorylation levels and phenotypic validation of our phosphoproteomic data suggested potential role of K8 site specific phosphorylation/dephosphorylation in neoplastic progression of A431 cells.

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

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Permanent Cell Line Cell

DISEASE(S): Skin Squamous Cell Carcinoma

SUBMITTER: Milind Vaidya  

LAB HEAD: Milind M Vaidya

PROVIDER: PXD005301 | Pride | 2018-07-05

REPOSITORIES: Pride