The PI‐3K/Akt/mTOR pathway regulates cell survival in a variety of tumor types including RCC and aberrant hyperactivation is a target for cancer therapy.51 An association between suppression of PI‐3K/Akt/mTORC pathway and STAT3 on inhibition of cell proliferation has been reported.52 Collectively, our data suggest a close connection between TNFR2/pSTAT3Ser727 signaling and VEGFR2/PI‐3K/Akt/mTORC pathways in driving survival of ccRCC‐CD133+CSCs. Here, PROM1 is linked to renal cell carcinoma.