Year: 2023
Type: article
Abstract: Metastasis of Lung adenocarcinoma (LUAD) is a major cause of death in patients. Aryl hydrocarbon receptor (AHR) is an important transcription factor involved in the initiation and progression of lung cancer. Polo-like kinase 1 (PLK1), a serine/threonine kinase, is an oncogene that promotes the malignancy of multiple cancer types. Nonetheless, the interaction between these two factors and significance in lung cancer remains to be determined. Here, we demonstrate that PLK1 phosphorylates AHR at S489 in LUAD, which leads to epithelial-mesenchymal transition (EMT) and metastatic events. RNA-seq analyses show that type 2 deiodinase (DIO2) is responsible for EMT and enhanced metastatic potential. DIO2 converts tetraiodothyronine (T4) to triiodothyronine (T3), which then activates thyroid hormone signaling. In vitro and in vivo experiments demonstrate that treatment with T3 or T4 promotes the metastasis of LUAD, whereas depletion of DIO2 or deiodinase inhibitor disrupts this property. Taken together, our results identify the phosphorylation of AHR by PLK1 as a mechanism leading to the progression of LUAD and provide possible therapeutic interventions for this event.
Source: PLoS Genetics
Institutions: University of Kentucky, Markey Cancer Center
Language: English
Topic: Cancer Cells and Metastasis
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,655
Awards: G5520316217, G6888208216, University of Kentucky Markey Cancer Center – Cancer Center Support Grant, Overcoming Drug Resistance of Castration-Resistant Prostate Cancer, Enhancing the efficacy of androgen signaling inhibitors in prostate cancer, Improving chemotherapy of castration-resistant prostate cancer., Plk1 as a prognostic biomarker for prostate cancer, Targeting Polo-Like Kinase 1 in Prostate Cancer to Enhance Therapeutic Efficacy
OpenAlex ID: W4388858854