Abstract
Abstract 3177: Angiopoietin-like 4 suppress clear cell renal cell carcinoma via inhibition lysosomal acid lipase
Cancer research (Chicago, Ill.), Vol.84(6_Supplement), pp.3177-3177
03/22/2024
DOI: 10.1158/1538-7445.AM2024-3177
Abstract
Abstract Renal cell carcinomas(RCC) account for about 76,000 new cancer cases annually in the U.S. and 403,000 cases world wide. Clear cell RCC (ccRCC) is both the most common and aggressive subtype, accounting for 75-85% of cases with a 5-year survival rate of 50-69% for all cases and only 10% for metastatic disease. In our study, we report thatANGPTL4 is highly upregulated in ccRCC compared to other types of cancers and normal kidney tissues. However, we identified a cohort of patients with significantly lower expression of ANGPTL4 which had a worse prognosis compared to rest of the patients with higher expression of ANGPTL4. This subset of patients had a lower frequency of mutated VHL and were enriched for genes related to lipid metabolism. In transplant tumor models using RCC cell lines with wild-type VHL, we found that ANGPTL4 suppresses tumor growth. Moreover, loss of ANGPTL4 in ccRCC cell lines reduces colony formation in a lysosomal acid lipase (LAL) dependent manner, a phenotype that is rescued by expression of nANGPTL4. This data indicates that ANGPTL4 suppresses ccRCC tumors in a cancer cell intrinsic manner via regulation of LAL activity. This cohort of patients with low ANGPTL4 may be more dependent on lipid metabolism and less likely to respond to anti-angiogenic TKI plus immune checkpoint inhibitor therapy. Citation Format: Zeng Jin, Umasankar De, Tanzia Tithi, Jeremy Kleberg, Akhila Nataraj, Elena Jolley, Brandon Davies, Weizhou Zhang, Ryan Kolb. Angiopoietin-like 4 suppress clear cell renal cell carcinoma via inhibition lysosomal acid lipase [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3177.
Details
- Title: Subtitle
- Abstract 3177: Angiopoietin-like 4 suppress clear cell renal cell carcinoma via inhibition lysosomal acid lipase
- Creators
- Zeng Jin - Florida CollegeUmasankar De - Florida CollegeTanzia Tithi - University of FloridaJeremy Kleberg - Florida CollegeAkhila Nataraj - Florida CollegeElena Jolley - Florida State UniversityBrandon Davies - University of IowaWeizhou Zhang - University of FloridaRyan Kolb - University of Florida
- Resource Type
- Abstract
- Publication Details
- Cancer research (Chicago, Ill.), Vol.84(6_Supplement), pp.3177-3177
- DOI
- 10.1158/1538-7445.AM2024-3177
- ISSN
- 1538-7445
- eISSN
- 1538-7445
- Language
- English
- Date published
- 03/22/2024
- Academic Unit
- Fraternal Order of Eagles Diabetes Research Center; Biochemistry and Molecular Biology
- Record Identifier
- 9984647960102771
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