TY - JOUR
T1 - Aldehyde Dehydrogenase 1B1 Is Associated with Altered Cell Morphology, Proliferation, Migration and Chemosensitivity in Human Colorectal Adenocarcinoma Cells
AU - Tsochantaridis, Ilias
AU - Roupas, Angelos
AU - Voulgaridou, Georgia-Persephoni
AU - Giatromanolaki, Alexandra
AU - Koukourakis, Michael I
AU - Panayiotidis, Mihalis I
AU - Pappa, Aglaia
N1 - 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.
PY - 2021/1/6
Y1 - 2021/1/6
N2 - 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.
AB - 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.
KW - ALDH
KW - ALDH1B1
KW - Aldehyde dehydrogenase
KW - Cancer
KW - Cell cycle
KW - Cell morphology
KW - Cell proliferation
KW - Chemoresistance
KW - HT29
KW - Migration
UR - http://www.scopus.com/inward/record.url?scp=85099742699&partnerID=8YFLogxK
U2 - 10.3390/biomedicines9010044
DO - 10.3390/biomedicines9010044
M3 - Article
C2 - 33419031
SN - 2227-9059
VL - 9
SP - 1
EP - 20
JO - Biomedicines
JF - Biomedicines
IS - 1
M1 - 44
ER -
