Dataset Information

FAS Inhibited Proteomics and Phosphoproteomics Profiling of Colorectal Cancer Spheroids shows Activation of Ferroptotic Death Mechanism

ABSTRACT: Colorectal cancer (CRC) is projected to become the third most diagnosed and third most fatal cancer in the United States by 2024, with early onset CRC on the rise. Research is constantly underway to discover novel therapeutics for the treatment of various cancers to improve patient outcomes and survival rates. Recently, fatty acid synthase (FAS) has become a druggable target of interest for the treatment of many different cancers. FAS inhibitors have been developed over the years with mixed success. One such inhibitor, TVB-2640, has gained popularity for its high specificity for FAS and has even entered a phase 1 clinical trial for the treatment of solid tumors. However, the distinct molecular differences that occur upon inhibiting FAS have yet to be understood. Here, we conduct time course proteomics and phosphoproteomics on analyses HCT 116 and HT-29 CRC spheroids inhibited with either a generation 1 (cerulenin) or generation 2 (TVB-2640) FAS inhibitor. Proteins involved in lipid metabolism and cellular respiration were altered in abundance. It was also observed that proteins and enzymes involved in ferroptosis—an iron mediated form of cell death—were altered. These results show HT-29 spheroids exposed to cerulenin or TVB-2640 are undergoing a ferroptotic death mechanism.

INSTRUMENT(S): Q Exactive HF

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Epithelial Cell, Cell Culture

DISEASE(S): Colon Cancer

SUBMITTER: Brian Fries

LAB HEAD: Amanda B. Hummon

PROVIDER: PXD050987 | Pride | 2024-08-10

REPOSITORIES: Pride

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Dataset's files

Source:

			Action	DRS
	202308028_HT29_TVB_0Hr_Phos_02.mzML.thesaurus.txt.Phosphorylation.thesaurus.elib	Mzml
	202308028_HT29_TVB_0Hr_Phos_02.raw	Raw
	20230828_HCT116_Cer_0Hr_Phos_01.mzML.thesaurus.txt.Phosphorylation.thesaurus.elib	Mzml
	20230828_HCT116_Cer_0Hr_Phos_01.raw	Raw
	20230828_HCT116_Cer_0Hr_Phos_02.mzML.thesaurus.txt.Phosphorylation.thesaurus.elib	Mzml

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FAS Inhibited Proteomics and Phosphoproteomics Profiling of Colorectal Cancer Spheroids Shows Activation of Ferroptotic Death Mechanism.

Fries Brian D BD Hummon Amanda B AB

Journal of proteome research 20240730 9

Colorectal cancer (CRC) is projected to become the third most diagnosed and third most fatal cancer in the United States by 2024, with early onset CRC on the rise. Research is constantly underway to discover novel therapeutics for the treatment of various cancers to improve patient outcomes and survival. Fatty acid synthase (FAS) has become a druggable target of interest for the treatment of many different cancers. One such inhibitor, TVB-2640, has gained popularity for its high specificity for ...[more]

PMID: 39079039

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