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Article

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

by
Ilias Tsochantaridis
1,
Angelos Roupas
1,
Georgia-Persephoni Voulgaridou
1,
Alexandra Giatromanolaki
2,
Michael I. Koukourakis
3,
Mihalis I. Panayiotidis
4,5,6 and
Aglaia Pappa
1,*
1
Department of Molecular Biology & Genetics, Democritus University of Thrace, 68100 Alexandroupolis, Greece
2
Department of Pathology, University General Hospital of Alexandroupolis, Democritus University of Thrace, 68100 Alexandroupolis, Greece
3
Radiotherapy/Oncology, Radiobiology & Radiopathology Unit, Department of Medicine, School of Health Sciences, Democritus University of Thrace, 68100 Alexandroupolis, Greece
4
Department of Electron Microscopy & Molecular Pathology, The Cyprus Institute of Neurology & Genetics, Nicosia 2371, Cyprus
5
The Cyprus School of Molecular Medicine, The Cyprus Institute of Neurology & Genetics, Nicosia 1683, Cyprus
6
Department of Applied Sciences, Northumbria University, Newcastle Upon Tyne NE1 8ST, UK
*
Author to whom correspondence should be addressed.
Biomedicines 2021, 9(1), 44; https://doi.org/10.3390/biomedicines9010044
Submission received: 12 November 2020 / Revised: 29 December 2020 / Accepted: 31 December 2020 / Published: 6 January 2021
(This article belongs to the Section Cancer Biology and Oncology)

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 ZEB1 and vimentin and the consequent downregulation of E-cadherin. 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.
Keywords: aldehyde dehydrogenase; ALDH; ALDH1B1; HT29; cell proliferation; cell morphology; chemoresistance; cell cycle; migration; cancer aldehyde dehydrogenase; ALDH; ALDH1B1; HT29; cell proliferation; cell morphology; chemoresistance; cell cycle; migration; cancer
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MDPI and ACS Style

Tsochantaridis, I.; Roupas, A.; Voulgaridou, G.-P.; Giatromanolaki, A.; Koukourakis, M.I.; Panayiotidis, M.I.; Pappa, A. Aldehyde Dehydrogenase 1B1 Is Associated with Altered Cell Morphology, Proliferation, Migration and Chemosensitivity in Human Colorectal Adenocarcinoma Cells. Biomedicines 2021, 9, 44. https://doi.org/10.3390/biomedicines9010044

AMA Style

Tsochantaridis I, Roupas A, Voulgaridou G-P, Giatromanolaki A, Koukourakis MI, Panayiotidis MI, Pappa A. Aldehyde Dehydrogenase 1B1 Is Associated with Altered Cell Morphology, Proliferation, Migration and Chemosensitivity in Human Colorectal Adenocarcinoma Cells. Biomedicines. 2021; 9(1):44. https://doi.org/10.3390/biomedicines9010044

Chicago/Turabian Style

Tsochantaridis, Ilias, Angelos Roupas, Georgia-Persephoni Voulgaridou, Alexandra Giatromanolaki, Michael I. Koukourakis, Mihalis I. Panayiotidis, and Aglaia Pappa. 2021. "Aldehyde Dehydrogenase 1B1 Is Associated with Altered Cell Morphology, Proliferation, Migration and Chemosensitivity in Human Colorectal Adenocarcinoma Cells" Biomedicines 9, no. 1: 44. https://doi.org/10.3390/biomedicines9010044

APA Style

Tsochantaridis, I., Roupas, A., Voulgaridou, G.-P., Giatromanolaki, A., Koukourakis, M. I., Panayiotidis, M. I., & Pappa, A. (2021). Aldehyde Dehydrogenase 1B1 Is Associated with Altered Cell Morphology, Proliferation, Migration and Chemosensitivity in Human Colorectal Adenocarcinoma Cells. Biomedicines, 9(1), 44. https://doi.org/10.3390/biomedicines9010044

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