KLF4α stimulates breast cancer cell proliferation by acting as a KLF4 antagonist
| Autor: | Martin Degen, Ruth Chiquet-Ehrismann, Jacqueline Ferralli |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
tumors
0301 basic medicine Gene isoform Pathology medicine.medical_specialty proliferation Kruppel-Like Transcription Factors 610 Medicine & health Breast Neoplasms medicine.disease_cause Kruppel-Like Factor 4 alternative splicing 03 medical and health sciences 0302 clinical medicine Breast cancer stomatognathic system Cell Line Tumor medicine Humans Protein Isoforms Transcription factor Cell Proliferation Cell growth business.industry fungi Alternative splicing medicine.disease KLF4 Cell Transformation Neoplastic 030104 developmental biology Oncology Cytoplasm 030220 oncology & carcinogenesis embryonic structures KLF4α/KLF4(FL) ratio Cancer research Female sense organs biological phenomena cell phenomena and immunity Carcinogenesis business Research Paper |
| Zdroj: | Oncotarget Ferralli, Jacqueline; Chiquet-Ehrismann, Ruth; Degen, Martin (2016). KLF4α stimulates breast cancer cell proliferation by acting as a KLF4 antagonist. OncoTarget, 7(29), pp. 45608-45621. Impact Journals LLC 10.18632/oncotarget.10058 |
| ISSN: | 1949-2553 |
| DOI: | 10.18632/oncotarget.10058 |
| Popis: | Krüppel-like factor 4 (KLF4), a transcription factor involved in both tumor suppression and oncogenesis in various human tumors, is subject to alternative splicing that produces KLF4α. KLF4α is primarily expressed in the cytoplasm because it lacks exon 3 of KLF4, which contains the nuclear localization signal. The role of KLF4 in breast cancer remains unclear and nothing is known yet about the expression and function of the isoform KLF4α. Here, we show that KLF4α is expressed in normal and tumoral tissue of the breast and provide evidence that the KLF4α/KLF4(full-length) (FL) ratio is increased in tumors compared to corresponding normal tissue. Forced increase of the KLF4α/KLF4(FL) ratio in the metastatic breast cancer cell line MDA-MB-231 decreases the levels of E-Cadherin, p21Cip1, and p27Kip1, three known KLF4(FL) target genes, and stimulates cell proliferation. We suggest that cytoplasmic KLF4α binds to KLF4(FL) and retains it in the cytoplasm thereby antagonizing the gene regulatory activities of KLF4(FL) in the nucleus. Our results establish KLF4α as a KLF4 isoform that opposes the function of KLF4(FL) and as an important factor in the complex and unresolved role of KLF4(FL) in breast carcinogenesis. |
| Databáze: | OpenAIRE |
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