Journal
SCIENCE TRANSLATIONAL MEDICINE
Volume 8, Issue 361, Pages -Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/scitranslmed.aaf8127
Keywords
-
Categories
Funding
- Cancer Prevention Research Institute of Texas grants [RP130189, RP160180]
- NIH [C06 RR30414]
- Simmons Cancer Center [5P30 CA142543-03, 1P01CA95471-09]
- UT Southwestern [5P30 CA142543-03, 1P01CA95471-09]
- Institute for Innovations in Medicine
- Harold C. Simmons Cancer Center Startup Award
- Disease Oriented Clinical Scholar award
- Damon Runyon Clinical Investigator award [CI-68-13]
- Welch Foundation [I-1879]
- Robert A. Welch Foundation [I-1422]
- National Research Foundation of Korea [NRF-2015K2A1A2069549]
Ask authors/readers for more resources
Mutations in the adenomatous polyposis coli (APC) gene are common in colorectal cancer (CRC), and more than 90% of those mutations generate stable truncated gene products. We describe a chemical screen using normal human colonic epithelial cells (HCECs) and a series of oncogenically progressed HCECs containing a truncated APC protein. With this screen, we identified a small molecule, TASIN-1 (truncated APC selective inhibitor-1), that specifically kills cells with APC truncations but spares normal and cancer cells with wild-type APC. TASIN-1 exerts its cytotoxic effects through inhibition of cholesterol biosynthesis. In vivo administration of TASIN-1 inhibits tumor growth of CRC cells with truncated APC but not APC wild-type CRC cells in xenograft models and in a genetically engineered CRC mouse model with minimal toxicity. TASIN-1 represents a potential therapeutic strategy for prevention and intervention in CRC with mutant APC.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available