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Agbo et al. J Cancer Metastasis Treat 2019;5:77 Journal of Cancer
DOI: 10.20517/2394-4722.2019.35 Metastasis and Treatment

Original Article Open Access

Loss of the Krüppel-like factor 4 tumor suppressor
is associated with epithelial-mesenchymal transition

in colorectal cancer

Kimberley C. Agbo , Jessie Z. Huang , Amr M. Ghaleb , Jennie L. Williams , Kenneth R. Shroyer ,
3
2
2
1,#
1,#
Agnieszka B. Bialkowska , Vincent W. Yang 1,4
1
1 Department of Medicine, Stony Brook University School of Medicine, Stony Brook, NY 11794, USA.
2 Department of Pathology, Stony Brook University School of Medicine, Stony Brook, NY 11794, USA.
3 Department of Family, Population and Preventive Medicine, Stony Brook, NY 11794, USA.
4 Department of Physiology and Biophysics, Stony Brook University School of Medicine, Stony Brook, NY 11794, USA.
# Authors contributed equally.
Correspondence to: Dr. Vincent W. Yang, Department of Medicine, Stony Brook University School of Medicine, HSC T-16, Rm
020, Stony Brook, NY 11794, USA. E-mail: vincent.yang@stonybrookmedicine.edu
How to cite this article: Agbo KC, Huang JZ, Ghaleb AM, Williams JL, Shroyer KR, Bialkowska AB, Yang VW. Loss of the Krüppel-
like factor 4 tumor suppressor is associated with epithelial-mesenchymal transition in colorectal cancer. J Cancer Metastasis
Treat 2019;5:77. http://dx.doi.org/10.20517/2394-4722.2019.35

Received: 11 Sep 2019 First Decision: 30 Oct 2019 Revised: 9 Nov 2019 Accepted: 14 Nov 2019 Published: 26 Nov 2019
Science Editor: William P. Schiemann Copy Editor: Jing-Wen Zhang Production Editor: Jing Yu

Abstract

Aim: Colorectal cancer (CRC) is the third leading cancer-related cause of death due to its propensity to metastasize.
Epithelial-mesenchymal transition (EMT) is a multistep process important for invasion and metastasis of CRC.
Krüppel-like factor 4 (KLF4) is a zinc finger transcription factor highly expressed in differentiated cells of the
intestinal epithelium. KLF4 has been shown to play a tumor suppressor role during CRC tumorigenesis - its loss
accelerates development and progression of cancer. The present study examined the relationship between KLF4
and markers of EMT in CRC.

Methods: Immunofluorescence staining for KLF4 and EMT markers was performed on archived patient samples
after colorectal cancer resection and on colonic tissues of mice with colitis-associated cancer.

Results: We found that KLF4 expression is lost in tumor sections obtained from CRC patients and in those of
mouse colon following azoxymethane and dextran sodium sulfate (AOM/DSS) treatment when compared to
their respective normal appearing mucosa. Importantly, in CRC patient tumor sections, we observed a negative
correlation between KLF4 levels and mesenchymal markers including TWIST, β-catenin, claudin-1, N-cadherin, and

© The Author(s) 2019. Open Access This article is licensed under a Creative Commons Attribution 4.0
International License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use,
sharing, adaptation, distribution and reproduction in any medium or format, for any purpose, even commercially, as long
as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license,
and indicate if changes were made.

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