A chemical biology screen identifies a vulnerability of neuroendocrine cancer cells to SQLE inhibition.

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 Commun

journal_title

Nature communications

authors

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/s41467-018-07959-4

subject

Has Abstract

pub_date

2019-01-09 00:00:00

pages

96

issue

1

issn

2041-1723

pii

10.1038/s41467-018-07959-4

journal_volume

10

pub_type

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