Zhang, J.; Chen, Z.; Mao, Y.; He, Y.; Wu, X.; Wu, J.; Sheng, L. ID2 Promotes Lineage Transition of Prostate Cancer through FGFR and JAK-STAT Signaling. Cancers2024, 16, 392.
Zhang, J.; Chen, Z.; Mao, Y.; He, Y.; Wu, X.; Wu, J.; Sheng, L. ID2 Promotes Lineage Transition of Prostate Cancer through FGFR and JAK-STAT Signaling. Cancers 2024, 16, 392.
Zhang, J.; Chen, Z.; Mao, Y.; He, Y.; Wu, X.; Wu, J.; Sheng, L. ID2 Promotes Lineage Transition of Prostate Cancer through FGFR and JAK-STAT Signaling. Cancers2024, 16, 392.
Zhang, J.; Chen, Z.; Mao, Y.; He, Y.; Wu, X.; Wu, J.; Sheng, L. ID2 Promotes Lineage Transition of Prostate Cancer through FGFR and JAK-STAT Signaling. Cancers 2024, 16, 392.
Abstract
The use of ARPIs has led to an increase in the proportion of AR-null prostate cancer, including NEPC and DNPC, but the mechanism underlying this lineage transition has not been elucidated. We found that ID2 expression was increased in AR-null prostate cancer. In vitro and in vivo studies confirmed that ID2 promotes PCa malignancy and can confer resistance to enzalutamide in PCa cells. We generated a ID2 UP50 signature, which is capable to determine resistance to enzalutamide and also valuable for predicting patient prognosis. Functional experiments showed that ID2 could activate the stemness-associated JAK/STAT and FGFR signaling while inhibiting the AR signaling pathway. Our study indicates that ID2 promotes the acquisition of a stem-like phenotype in adenocarcinoma cells, leading to resistance to ADT and next-generation ARPIs in prostate cancer.
Keywords
lineage transition; prostate cancer; ID2; NEPC and DNPC
Subject
Biology and Life Sciences, Cell and Developmental Biology
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
