Depletion of Keratin8 affects tumorigenic potential of A431 cells via altering multiple signaling pathways

ABSTRACT: Keratins are the largest subgroup of intermediate filament proteins which are expressed in a tissue specific and differentiation state dependent manner. Apart from their mechanical functions, they have been shown to perform various regulatory roles. Most of these functions have been studied on keratin pair of 8/18 (K8/18) which is preferentially expressed in simple epithelia. The aberrant expression of this keratin pair has been correlated with increased invasiveness and poor prognosis of various squamous cell carcinomas (SCCs) including Skin SSCs. However the exact role it’s of aberrant expression in skin SCCs and associated mechanism remains elusive. To understand the role of K8/18 in skin SCC, ShRNA based stable K8 knockdown clones were generated in skin epidermoid carcinoma derived A431 cells which resulted in the decreased tumorigenic potential of these cells. Next, to decipher the molecular basis behind K8 mediated regulation of tumorigenic potential of A431 cells, TMT based total quantitative proteomics was performed for vector control and K8 knockdown clones (K8KD1/K8KD2). There were a total of 2952 proteins detected in the TMT based total quantitative proteomics, out of which, K8KD1 clone showed 140 proteins to be differentially expressed, whereas K8KD2 clone showed 119 proteins to be differentially expressed in comparison to vector control cells. Further, functional analysis of our data showed involvement of cell death and survival together with cellular movement pathway to be affected upon K8 knockdown. Altogether, the present data potentiates the role of K8 in neoplastic progression of skin SCC, together with the possible mechanism underlying the same.

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

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Permanent Cell Line Cell

DISEASE(S): Squamous Cell Carcinoma Of The Skin

SUBMITTER: Milind Vaidya  

LAB HEAD: Milind M Vaidya

PROVIDER: PXD007206 | Pride | 2018-02-27

REPOSITORIES: Pride