KLF4α stimulates breast cancer cell proliferation by acting as a KLF4 antagonist.

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

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > School of Dental Medicine > School of Dental Medicine, Orthodontic Research

UniBE Contributor:

Degen, Martin

Subjects:

600 Technology > 610 Medicine & health

ISSN:

1949-2553

Publisher:

Impact Journals LLC

Language:

English

Submitter:

Eveline Carmen Schuler

Date Deposited:

08 May 2017 08:16

Last Modified:

08 May 2017 08:16

Publisher DOI:

10.18632/oncotarget.10058

PubMed ID:

27323810

Uncontrolled Keywords:

KLF4 KLF4α/KLF4(FL) Ratio, alternative splicing, Proliferation, tumors

BORIS DOI:

10.7892/boris.93960

URI:

https://boris.unibe.ch/id/eprint/93960

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