Deletion of Lats1/2 in adult kidney epithelia leads to renal cell carcinoma.
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ABSTRACT:
SUBMITTER: Carter P
PROVIDER: S-EPMC8159698 | biostudies-literature | 2021 Jun
REPOSITORIES: biostudies-literature
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Deletion of Lats1/2 in adult kidney epithelia leads to renal cell carcinoma.
Carter Phoebe P Schnell Ulrike U Chaney Christopher C Tong Betty B Pan Xinchao X Ye Jianhua J Mernaugh Glenda G Cotton Jennifer L JL Margulis Vitaly V Mao Junhao J Zent Roy R Evers Bret M BM Kapur Payal P Carroll Thomas J TJ
The Journal of clinical investigation 20210601 11
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2021-01-15 | GSE164879 | GEO
Project description:Deletion of Lats1/2 in adult kidney epithelia leads to renal cell carcinoma
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Project description:The most common type of kidney cancer in adults is renal cell carcinoma (RCC), which accounts for approximately 90% of cases. RCC is a variant disease with numerous subtypes; the most common subtype is clear cell RCC (ccRCC, 75%), followed by papillary RCC (pRCC, 10%) and chromophobe RCC (chRCC, 5%). To identify a genetic target for all subtypes, we analyzed The Cancer Genome Atlas (TCGA) databases of ccRCC, pRCC, and chromophobe RCC. Enhancer of zeste homolog 2 (EZH2), which encodes a methyltransferase, was observed to be significantly upregulated in tumors. The EZH2 inhibitor tazemetostat induced anticancer effects in RCC cells. TCGA analysis revealed that large tumor suppressor kinase 1 (LATS1), a key tumor suppressor of the Hippo pathway, was significantly downregulated in tumors; the expression of LATS1 was increased by tazemetostat. Through additional experiments, we confirmed that LATS1 plays a crucial role in EZH2 inhibition and has a negative association with EZH2. Therefore, we suggest that epigenetic control could be a novel therapeutic strategy for three subtypes of RCC.
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