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Cancer Lett. 2014 Nov 1;354(1):87-96. doi: 10.1016/j.canlet.2014.07.045. Epub 2014 Aug 8.

Gain-of-function of mutant p53: mutant p53 enhances cancer progression by inhibiting KLF17 expression in invasive breast carcinoma cells.

Author information

1
Institute of Biomedical Sciences, School of Life Sciences, East China Normal University, 500 Dongchuan Road, Shanghai, 200241, China. Electronic address: amjad_486@yahoo.com.
2
Institute of Biomedical Sciences, School of Life Sciences, East China Normal University, 500 Dongchuan Road, Shanghai, 200241, China.
3
Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China; Department of Biotechnology, Abdul Wali Khan University, Mardan, 23200, Pakistan. Electronic address: ahdayazb5@awkum.edu.pk.

Abstract

Kruppel-like-factor 17 (KLF17) is a negative regulator of metastasis and epithelial-mesenchymal-transition (EMT). However, its expression is downregulated in metastatic breast cancer that contains p53 mutations. Here, we show that mutant-p53 plays a key role to suppress KLF17 and thereby enhances cancer progression, which defines novel gain-of-function (GOF) of mutant-p53. Mutant-p53 interacts with KLF17 and antagonizes KLF17 mediated EMT genes transcription. Depletion of KLF17 promotes cell viability, decreases apoptosis and induces drug resistance in metastatic breast cancer cells. KLF17 suppresses cell migration and invasion by decreasing CD44, PAI-1 and Cyclin-D1 expressions. Taken together, our results show that KLF17 is important for the suppression of metastasis and could be a potential therapeutic target during chemotherapy.

KEYWORDS:

Breast cancer; Chemotherapy; Invasion; KLF17; Metastasis; Mutant p53

PMID:
25111898
DOI:
10.1016/j.canlet.2014.07.045
[Indexed for MEDLINE]

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