Tumor necrosis factor receptor-2 signaling pathways promote survival of cancer stem-like CD133⁺ cells in clear cell renal carcinoma.

ABSTRACT: Clear cell renal cell carcinoma (ccRCC) contains cancer stem-like cells (CSCs) that express CD133 (ccRCC-CD133⁺). CSCs are rarely in cell cycle and, as nonproliferating cells, resist most chemotherapeutic agents. Previously, we reported that tumor necrosis factor receptor-2 (TNFR2) signaling promotes the cell cycle entry of ccRCC-CD133⁺CSCs, rendering them susceptible to cell-cycle-dependent chemotherapeutics. Here, we describe a TNFR2-activated signaling pathway in ccRCC-^CD133+CSCs that is required for cell survival. Wild-type (wt)TNF or R2TNF but not R1TNF (TNF muteins that selectively bind to TNFR2 and TNFR1) induces phosphorylation of signal transducer and activator of transcription 3 (STAT3) on serine⁷²⁷ but not tyrosine⁷⁰⁵, resul

SUBMITTER: Bradley JR 

PROVIDER: S-EPMC7003657 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature