Abstract:
:Aberrant metabolism of cancer cells is well appreciated, but the identification of cancer subsets with specific metabolic vulnerabilities remains challenging. We conducted a chemical biology screen and identified a subset of neuroendocrine tumors displaying a striking pattern of sensitivity to inhibition of the cholesterol biosynthetic pathway enzyme squalene epoxidase (SQLE). Using a variety of orthogonal approaches, we demonstrate that sensitivity to SQLE inhibition results not from cholesterol biosynthesis pathway inhibition, but rather surprisingly from the specific and toxic accumulation of the SQLE substrate, squalene. These findings highlight SQLE as a potential therapeutic target in a subset of neuroendocrine tumors, particularly small cell lung cancers.
journal_name
Nat Communjournal_title
Nature communicationsauthors
Mahoney CE,Pirman D,Chubukov V,Sleger T,Hayes S,Fan ZP,Allen EL,Chen Y,Huang L,Liu M,Zhang Y,McDonald G,Narayanaswamy R,Choe S,Chen Y,Gross S,Cianchetta G,Padyana AK,Murray S,Liu W,Marks KM,Murtie J,Dorsch M,doi
10.1038/s41467-018-07959-4subject
Has Abstractpub_date
2019-01-09 00:00:00pages
96issue
1issn
2041-1723pii
10.1038/s41467-018-07959-4journal_volume
10pub_type
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