The CDK4/6 inhibitors dephosphorylate RNF26 to stabilize TSC1 and increase the sensitivity of ccRCC to anti-angiogenesis drug

It has been reported that the combined use of CDK4/6 inhibitors and mTOR inhibitors has achieved some clinical success in renal cell carcinoma. Therefore, exploring the underlying mechanism of CDK4/6 pathway in cancer cells and the drug interaction of CDK4/6 inhibitors in combination therapy would helpful find new therapeutic strategies for ccRCC.

In studies, we intended to explore the mechanism of how CDK4/6 inhibitors increased the protein expression of TSC1 in ccRCC. We demonstrated that the CDK4/6 inhibitors stabilized TSC1 in ccRCC cells. Then, we showed that e3 ligase RNF26 interacted with TSC1 to promote the degradation of TSC1 and activate the mTOR signaling pathway in ccRCC.