Article (Scientific journals)
Tumor suppressive p53 signaling empowers metastatic inhibitor KLF17-dependent transcription to overcome tumorigenesis in non-small cell lung cancer.
Ali, Amjad; Zeeshan Bhatti, Muhammad; Saboor, Shah A et al.
2015In Journal of Biological Chemistry
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Keywords :
p53; klf17; metastasis
Abstract :
[en] Metastasis, which is controlled by concerted action of multiple genes, is a complex process, and is important cause of cancer death. KLF17 is a negative regulator of metastasis and epithelial-mesenchymal-transition (EMT) during cancer progression. However, the underlying molecular mechanism and biological relevance of KLF17 in cancer cells are poorly understood. Here, we show that tumor suppressor protein p53 plays an integral role to induce KLF17 expression in NSCLC. p53 is recruited to KLF17 promoter and results in the formation of p53-DNA complex. p53 enhances binding of p300, and favors histone acetylation on KLF17 promoter. Mechanistically, p53 physically interacts with KLF17 and thereby enhances anti-metastatic function of KLF17. p53 empowers KLF17 mediated EMT genes transcription via enhancing physical association of KLF17 to target gene promoters. Nutlin-3 recruits KLF17 to EMT target gene promoters and results in the formation of KLF17-DNA complex via p53-dependent pathway. p53 depletion abrogates DNA binding affinity of KLF17 to EMT target gene promoters. KLF17 is critical for p53 cellular activities in NSCLC. Importantly, KLF17 enhances p53 transcription to generate a novel positive feedback loop. KLF17 depletion accelerates lungs cancer cells growth in response to chemotherapy. Mechanistically, we found that KLF17 increases tumor suppressor genes p53, p21 and pRB expressions in NSCLC. Functionally, KLF17 required p53 to suppress cancer cell invasion and migration in NSCLC. In sum, our study highlights novel insight into anti-EMT affect of KLF17 via p53-dependent pathway in NSCLC, and KLF17 may be a new therapeutic target in NSCLC with p53 status.
Disciplines :
Biochemistry, biophysics & molecular biology
Author, co-author :
Ali, Amjad ;  Université de Liège > Département de pharmacie > Chimie médicale
Zeeshan Bhatti, Muhammad
Saboor, Shah A
Duong, Hong Quan 
Huda Alkreathy, Mohammad
Mohammad, Shah Faisal
Ali, Rahmat
Ahmad, Ayaz
Language :
English
Title :
Tumor suppressive p53 signaling empowers metastatic inhibitor KLF17-dependent transcription to overcome tumorigenesis in non-small cell lung cancer.
Publication date :
24 April 2015
Journal title :
Journal of Biological Chemistry
ISSN :
0021-9258
eISSN :
1083-351X
Publisher :
American Society for Biochemistry and Molecular Biology, Baltimore, United States - Maryland
Peer reviewed :
Peer Reviewed verified by ORBi
Available on ORBi :
since 01 June 2015

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