Aldehyde Dehydrogenase 1B1 Is Associated with Altered Cell Morphology, Proliferation, Migration and Chemosensitivity in Human Colorectal Adenocarcinoma Cells

Tsochantaridis, Ilias, Roupas, Angelos, Voulgaridou, Georgia-Persephoni, Giatromanolaki, Alexandra, Koukourakis, Michael I., Panagiotidis, Mihalis and Pappa, Aglaia (2021) Aldehyde Dehydrogenase 1B1 Is Associated with Altered Cell Morphology, Proliferation, Migration and Chemosensitivity in Human Colorectal Adenocarcinoma Cells. Biomedicines, 9 (1). p. 44. ISSN 2227-9059

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Official URL: https://doi.org/10.3390/biomedicines9010044

Abstract

Aldehyde dehydrogenases (ALDHs) are NAD(P) -dependent enzymes that catalyze the oxidation of endogenous and exogenous aldehydes to their corresponding carboxylic acids. ALDHs participate in a variety of cellular mechanisms, such as metabolism, cell proliferation and apoptosis, as well as differentiation and stemness. Over the last few years, ALDHs have emerged as cancer stem cell markers in a wide spectrum of solid tumors and hematological malignancies. In this study, the pathophysiological role of ALDH1B1 in human colorectal adenocarcinoma was investigated. Human colon cancer HT29 cells were stably transfected either with human green fluorescent protein (GFP)-tagged ALDH1B1 or with an empty lentiviral expression vector. The overexpression of ALDH1B1 was correlated with altered cell morphology, decreased proliferation rate and reduced clonogenic efficiency. Additionally, ALDH1B1 triggered a G2/M arrest at 24 h post-cell synchronization, probably through p53 and p21 upregulation. Furthermore, ALDH1B1-overexpressing HT29 cells exhibited enhanced resistance against doxorubicin, fluorouracil (5-FU) and etoposide. Finally, ALDH1B1 induced increased migratory potential and displayed epithelial-mesenchymal transition (EMT) through the upregulation of and and the consequent downregulation of Taken together, ALDH1B1 confers alterations in the cell morphology, cell cycle progression and gene expression, accompanied by significant changes in the chemosensitivity and migratory potential of HT29 cells, underlying its potential significance in cancer progression.

Item Type: Article
Additional Information: Funding Information: Acknowledgments: The research work was supported by the Hellenic Foundation for Research and Innovation (HFRI) under the HFRI PhD Fellowship grant (Fellowship Number: 523). We thank Katerina Spyridopoulou of the OPENSCREEN-GR facility at Democritus University of Thrace for her help with flow cytometry analyses. We acknowledge the support of the M.Sc. course of Translational Research in Biomedicine (Department of Molecular Biology and Genetics, Democritus University of Thrace.
Uncontrolled Keywords: ALDH, ALDH1B1, HT29, aldehyde dehydrogenase, cancer, cell cycle, cell morphology, cell proliferation, chemoresistance, migration
Subjects: C100 Biology
C700 Molecular Biology, Biophysics and Biochemistry
C900 Others in Biological Sciences
Department: Faculties > Health and Life Sciences > Applied Sciences
Depositing User: Rachel Branson
Date Deposited: 25 Jan 2021 14:37
Last Modified: 25 Feb 2021 17:30
URI: http://nrl.northumbria.ac.uk/id/eprint/45299

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