Dataset Information

SILAC-based proteomic approach to delineate molecular alterations associated with erlotinib resistance in head and neck squamous cell carcinoma

ABSTRACT: Although Epidermal growth factor receptor (EGFR) is overexpressed in 90% of Head and neck squamous cell carcinoma (HNSCC) patients. Clinical trials with EGFR-targeted small molecule inhibitors such as erlotinib have shown a modest activity in recurrent or advanced HNSCC. To investigate the acquired mechanisms of erlotinib resistance we employed SILAC-based total proteomic analysis of an isogenic pair of erlotinib sensitive (SCC-S) and resistant (SCC-R) HNSCC cell line. This resulted in the identification of 5,427 proteins of which 532 proteins were overexpressed and 527 proteins were downregulated in SCC-R cells as compared to SCC-S cells (≥2 fold). Several proteins known to mediate erlotinib resistance in HNSCC and lung cancer were found to be dysregulated. Bioinformatics analysis of differentially expressed proteins showed enrichment of proteins involved in focal adhesion kinase (FAK) pathway downstream of EGFR. We identified CUB-domain containing protein 1 (CDCP1) and integrin β1 as upstream regulators of FAK signalling pathway to be overexpressed. We further demonstrated that CDCP1 and FAK can be targeted in combination as an alternative to erlotinib in HNSCC.

INSTRUMENT(S): Orbitrap Fusion

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Oral Epithelium

SUBMITTER: Harsha Gowda

LAB HEAD: Harsha Gowda

PROVIDER: PXD007768 | Pride | 2019-12-18

REPOSITORIES: Pride

ACCESS DATA

Dataset's files

Source:

Items per page:

1 - 5 of 25

Publications

MAP2K1 is a potential therapeutic target in erlotinib resistant head and neck squamous cell carcinoma.

Jain Ankit P AP Patel Krishna K Pinto Sneha S Radhakrishnan Aneesha A Nanjappa Vishalakshi V Kumar Manish M Raja Remya R Patil Arun H AH Kumari Anjali A Manoharan Malini M Karunakaran Coral C Murugan Saktivel S Keshava Prasad T S TS Chang Xiaofei X Mathur Premendu Prakash PP Kumar Prashant P Gupta Ravi R Gupta Rohit R Khanna-Gupta Arati A Sidransky David D Chatterjee Aditi A Gowda Harsha H

Scientific reports 20191211 1

Epidermal growth factor receptor (EGFR) targeted therapies have shown limited efficacy in head and neck squamous cell carcinoma (HNSCC) patients despite its overexpression. Identifying molecular mechanisms associated with acquired resistance to EGFR-TKIs such as erlotinib remains an unmet need and a therapeutic challenge. In this study, we employed an integrated multi-omics approach to delineate mechanisms associated with acquired resistance to erlotinib by carrying out whole exome sequencing, q ...[more]

PMID: 31827134

			Action	DRS
	ITID_TP_1.raw	Raw
	ITID_TP_10.raw	Raw
	ITID_TP_11.raw	Raw
	ITID_TP_12.raw	Raw
	ITID_TP_13.raw	Raw

Dataset Information

SILAC-based proteomic approach to delineate molecular alterations associated with erlotinib resistance in head and neck squamous cell carcinoma

Dataset's files

Publications

MAP2K1 is a potential therapeutic target in erlotinib resistant head and neck squamous cell carcinoma.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Similar Datasets

Genetic aberrations in MAP kinase pathway play an important role in erlotinib resistance in head and neck cancer
2019-12-18 | PXD007785 | Pride

SILAC-based quantitative tyrosine phosphoproteomic profiling identifies alternative therapeutic targets to erlotinib in head and neck squamous cell carcinoma
2022-10-13 | PXD007769 | Pride

Genome-wide gene expression analysis of EGFR inhibitor erlotinib-resistant and -sensitive head and neck squamous cell carcinoma cell lines Cal-27, SCC-25, FaDu, and SQ20B
2014-10-07 | GSE62061 | GEO

Genome-wide analysis of EGFR inhibitor erlotinib treatment in Head and neck, squamous cell carcinoma's FADU, SQ20B and Cal 27
2014-04-08 | E-GEOD-45891 | biostudies-arrayexpress

Charaterization of genetic alterations and gene expression signatures found in erlotinib-resistant and erlotinib/crizotinib dual-resistant HCC827 subpopulations
2014-10-07 | E-GEOD-62118 | biostudies-arrayexpress

SILAC proteomics analysis to discover effect sensors of EGFR inhibition
2018-10-18 | PXD005985 | Pride

Axl mediates acquired resistance of head and neck cancer cells to the epidermal growth factor receptor inhibitor erlotinib
2013-08-10 | E-GEOD-49135 | biostudies-arrayexpress

Microarray study to understand acquired resistance to EGFR-targeted therapy in lung cancer
2012-05-29 | E-GEOD-38310 | biostudies-arrayexpress

Expression data from EGFR WT or EGFR mutant NSCLC with or without erlotinib
2014-05-16 | E-GEOD-57156 | biostudies-arrayexpress

Targeted inhibition of human breast cancer cell lines selected as model systems of ERBB2-positive/EGFR high breast cancer [RPPA-HCC1954]
2012-10-22 | E-GEOD-36324 | biostudies-arrayexpress