MAP3K7-IKK inflammatory signaling modulates AR protein degradation and prostate cancer progression was written by Huang, Zhenlin;Tang, Bo;Yang, Yinhui;Yang, Zhaogang;Shi, Lei;Bai, Yang;Yan, Binyuan;Karnes, R. Jeffrey;Zhang, Jun;Jimenez, Rafael;Wang, Liguo;Wei, Qiang;Yang, Jinjian;Xu, Wanhai;Jia, Zhankui;Huang, Haojie. And the article was included in Cancer Research in 2021.Application of 524-12-9 The following contents are mentioned in the article:
Androgen receptor (AR) is a major survival factor for prostate cancer. Inflammation is implicated in many cancer types, including prostate cancer. Activation of MAP3K7 (also termed TAK1) and downstream IκB kinase β (IKKβ) by proinflammatory cytokines such as TNFα stimulates NF-κB survival pathways. Paradoxically, MAP3K7 is often deleted in human prostate cancer. Here, we demonstrate that AR protein expression is lower in inflammatory tumor areas compared with non-inflammatory tissues in patients with prostate cancer. Map3k7 knockout increased AR protein levels and activity in the mouse prostate, and MAP3K7 and AR protein levels were inversely correlated in prostate cancer patient specimens. TNFα treatment increased AR protein ubiquitination and proteasomal degradation Mechanistically, activation of IKKβ by TNFα induced phosphorylation and TRCP1/2 E3 ligase-mediated polyubiquitination and degradation of AR protein. TNFα suppressed prostate cancer proliferation, which could be rescued by blockade of AR degradation These findings reveal a previously unrecognized tumor suppressive function of the inflammation-activated MAP3K7-IKKβ axis in degrading AR protein. Moreover, they suggest that aberrant elevation of AR protein could be a prognostic biomarker and therapeutic target for MAP3K7-deficient prostate cancer. This study involved multiple reactions and reactants, such as 1,8,9-Trihydroxy-3-methoxy-6H-benzofuro[3,2-c]chromen-6-one (cas: 524-12-9Application of 524-12-9).
1,8,9-Trihydroxy-3-methoxy-6H-benzofuro[3,2-c]chromen-6-one (cas: 524-12-9) belongs to benzofurans derivatives. Benzofuran is a core structural unit found in many naturally occurring compounds with multidirectional biological activities. Introduction of benzofurans in organic synthesis, particularly drug synthesis, involves generally the use of their metalated species as nucleophiles in addition reactions or in metal-catalysed cross-coupling reactions.Application of 524-12-9
Referemce:
Benzofuran – Wikipedia,
Benzofuran | C8H6O – PubChem