Matches in SemOpenAlex for { <https://semopenalex.org/work/W4386944053> ?p ?o ?g. }
- W4386944053 abstract "Activation of the IκB kinase (IKK) complex has recurrently been linked to colorectal cancer (CRC) initiation and progression. However, identification of downstream effectors other than NF-κB has remained elusive. Here, analysis of IKK-dependent substrates in CRC cells after UV treatment revealed that phosphorylation of BRD4 by IKK-α is required for its chromatin-binding at target genes upon DNA damage. Moreover, IKK-α induces the NF-κB-dependent transcription of the cytokine LIF, leading to STAT3 activation, association with BRD4 and recruitment to specific target genes. IKK-α abrogation results in defective BRD4 and STAT3 functions and consequently irreparable DNA damage and apoptotic cell death upon different stimuli. Simultaneous inhibition of BRAF-dependent IKK-α activity, BRD4, and the JAK/STAT pathway enhanced the therapeutic potential of 5-fluorouracil combined with irinotecan in CRC cells and is curative in a chemotherapy-resistant xenograft model. Finally, coordinated expression of LIF and IKK-α is a poor prognosis marker for CRC patients. Our data uncover a functional link between IKK-α, BRD4, and JAK/STAT signaling with clinical relevance." @default.
- W4386944053 created "2023-09-23" @default.
- W4386944053 creator A5000320566 @default.
- W4386944053 creator A5004386682 @default.
- W4386944053 creator A5005083496 @default.
- W4386944053 creator A5017648269 @default.
- W4386944053 creator A5024957287 @default.
- W4386944053 creator A5035175323 @default.
- W4386944053 creator A5038627497 @default.
- W4386944053 creator A5050462003 @default.
- W4386944053 creator A5051681898 @default.
- W4386944053 creator A5052599318 @default.
- W4386944053 creator A5056070511 @default.
- W4386944053 creator A5056572870 @default.
- W4386944053 creator A5057028694 @default.
- W4386944053 creator A5060569859 @default.
- W4386944053 creator A5064766886 @default.
- W4386944053 creator A5073103018 @default.
- W4386944053 creator A5073899064 @default.
- W4386944053 creator A5076778474 @default.
- W4386944053 creator A5083387171 @default.
- W4386944053 creator A5089194201 @default.
- W4386944053 creator A5090276541 @default.
- W4386944053 creator A5092170030 @default.
- W4386944053 creator A5019647550 @default.
- W4386944053 date "2023-09-22" @default.
- W4386944053 modified "2023-10-18" @default.
- W4386944053 title "IκB kinase‐α coordinates BRD4 and JAK/STAT signaling to subvert DNA damage‐based anticancer therapy" @default.
- W4386944053 cites W1934094702 @default.
- W4386944053 cites W1984642649 @default.
- W4386944053 cites W1990879144 @default.
- W4386944053 cites W1992127633 @default.
- W4386944053 cites W2002513358 @default.
- W4386944053 cites W2014139160 @default.
- W4386944053 cites W2020541351 @default.
- W4386944053 cites W2028544780 @default.
- W4386944053 cites W2029275361 @default.
- W4386944053 cites W2029669343 @default.
- W4386944053 cites W2031211461 @default.
- W4386944053 cites W2042794591 @default.
- W4386944053 cites W2052692973 @default.
- W4386944053 cites W2057061888 @default.
- W4386944053 cites W2060267149 @default.
- W4386944053 cites W2064634958 @default.
- W4386944053 cites W2096673680 @default.
- W4386944053 cites W2106789440 @default.
- W4386944053 cites W2107398189 @default.
- W4386944053 cites W2108899869 @default.
- W4386944053 cites W2120572492 @default.
- W4386944053 cites W2122774148 @default.
- W4386944053 cites W2131413118 @default.
- W4386944053 cites W2133906887 @default.
- W4386944053 cites W2143819289 @default.
- W4386944053 cites W2146729875 @default.
- W4386944053 cites W2147049948 @default.
- W4386944053 cites W2150820945 @default.
- W4386944053 cites W2154941270 @default.
- W4386944053 cites W2170551349 @default.
- W4386944053 cites W2170830174 @default.
- W4386944053 cites W2171808845 @default.
- W4386944053 cites W2179438025 @default.
- W4386944053 cites W2230320310 @default.
- W4386944053 cites W2231865019 @default.
- W4386944053 cites W2341539131 @default.
- W4386944053 cites W2345356016 @default.
- W4386944053 cites W2346509327 @default.
- W4386944053 cites W2761133874 @default.
- W4386944053 cites W2784159027 @default.
- W4386944053 cites W2785761464 @default.
- W4386944053 cites W2791440239 @default.
- W4386944053 cites W2797814625 @default.
- W4386944053 cites W2888749522 @default.
- W4386944053 cites W2888766935 @default.
- W4386944053 cites W2896285889 @default.
- W4386944053 cites W2900679912 @default.
- W4386944053 cites W2918147447 @default.
- W4386944053 cites W2936677400 @default.
- W4386944053 cites W2946008330 @default.
- W4386944053 cites W2951675934 @default.
- W4386944053 cites W2961691917 @default.
- W4386944053 cites W3018442280 @default.
- W4386944053 cites W3113580855 @default.
- W4386944053 cites W3133943231 @default.
- W4386944053 cites W3138474425 @default.
- W4386944053 cites W3185669197 @default.
- W4386944053 cites W3216146155 @default.
- W4386944053 cites W4281759502 @default.
- W4386944053 cites W4310153812 @default.
- W4386944053 doi "https://doi.org/10.15252/embj.2023114719" @default.
- W4386944053 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/37737566" @default.
- W4386944053 hasPublicationYear "2023" @default.
- W4386944053 type Work @default.
- W4386944053 citedByCount "0" @default.
- W4386944053 crossrefType "journal-article" @default.
- W4386944053 hasAuthorship W4386944053A5000320566 @default.
- W4386944053 hasAuthorship W4386944053A5004386682 @default.
- W4386944053 hasAuthorship W4386944053A5005083496 @default.
- W4386944053 hasAuthorship W4386944053A5017648269 @default.
- W4386944053 hasAuthorship W4386944053A5019647550 @default.
- W4386944053 hasAuthorship W4386944053A5024957287 @default.