Dataset Information

Mevalonate pathway activity is a key determinant of radiation sensitivity in head and neck cancer

ABSTRACT: Radioresistance is a major hurdle in the treatment of head and neck squamous cell carcinoma (HNSCC). Here we report a novel role for statin-based treatment of HNSCCs as an actionable and safe adjuvant to radiotherapy. Proteomic profiling and comparison of radiosensitive and radioresistant HNSCCs revealed differential regulation of the mevalonate biosynthetic pathway. Consistent with this finding, inhibition of the mevalonate pathway by pitavastatin (and other related statins) sensitized SQ20B cells to ionizing radiation (IR) and reduced their clonogenic potential. In an effort to uncover the mechanism behind this statin-mediated sensitization, we analyzed prenylation of several important cellular targets upon combined IR-statin treatment. Overall, this study reinforces the view that the mevalonate pathway is a promsing novel therapeutic target in radioresistant HSNCCs.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Permanent Cell Line Cell

DISEASE(S): Head And Neck Cancer

SUBMITTER: Donald Wolfgeher

LAB HEAD: Dr. Stephen J Kron

PROVIDER: PXD007188 | Pride | 2019-06-25

REPOSITORIES: Pride

ACCESS DATA

Dataset's files

Source:

			Action	DRS
	160107_SPROT_Human_Iso_UP000005640.fasta	Fasta
	160208_SvR2_Gel.pptx	Other
	160323_SvR_Maxquant_Results.zip	Other
	160328_SvR2_proteinGroups_Final.xlsx	Xlsx
	170801_SvR.sf3	Other

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Publications

Mevalonate pathway activity as a determinant of radiation sensitivity in head and neck cancer.

Ricco Natalia N Flor Amy A Wolfgeher Don D Efimova Elena V EV Ramamurthy Aishwarya A Appelbe Oliver K OK Brinkman Jacqueline J Truman Andrew W AW Spiotto Michael T MT Kron Stephen J SJ

Molecular oncology 20190726 9

Radioresistance is a major hurdle in the treatment of head and neck squamous cell carcinoma (HNSCC). Here, we report that concomitant treatment of HNSCCs with radiotherapy and mevalonate pathway inhibitors (statins) may overcome resistance. Proteomic profiling and comparison of radioresistant to radiosensitive HNSCCs revealed differential regulation of the mevalonate biosynthetic pathway. Consistent with this finding, inhibition of the mevalonate pathway by pitavastatin sensitized radioresistant ...[more]

PMID: 31225926

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