Lactylation-Driven HECTD2 Limits the Response of Hepatocellular Carcinoma to Lenvatinib.

ABSTRACT: Drug resistance remains a major hurdle for the therapeutic efficacy of lenvatinib in hepatocellular carcinoma (HCC). However, the underlying mechanisms remain largely undetermined. Unbiased proteomic screening is performed to identify the potential regulators of lenvatinib resistance in HCC. Patient-derived organoids, patient-derived xenograft mouse models, and DEN/CCl₄ induced HCC models are constructed to evaluate the effects of HECTD2 both in vitro and in vivo. HECTD2 is found to be highly expressed in lenvatinib-resistant HCC cell lines, patient tissues, and patient-derived organoids and xenografts. In vitro and in vivo experiments demonstrated that overexpression of HECTD2 limits the response of HCC to lenvatinib treatment. Mechanistically, HECTD2 functions as an E3 ubiquit

SUBMITTER: Dong R 

PROVIDER: S-EPMC12005811 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature