Aldolase A promotes epithelial-mesenchymal transition to increase malignant potentials of cervical adenocarcinoma.
Adenocarcinoma
/ mortality
Cell Line, Tumor
Cell Movement
/ genetics
Cell Proliferation
/ genetics
Cervix Uteri
/ pathology
Disease-Free Survival
Epithelial-Mesenchymal Transition
Feedback, Physiological
Female
Fructose-Bisphosphate Aldolase
/ genetics
Gene Expression Regulation, Neoplastic
Gene Knockdown Techniques
Humans
Hypoxia-Inducible Factor 1, alpha Subunit
/ genetics
Kaplan-Meier Estimate
Prognosis
RNA, Small Interfering
/ metabolism
Signal Transduction
/ genetics
Uterine Cervical Neoplasms
/ mortality
aldolase A
cervical adenocarcinoma
epithelial-mesenchymal transition
hypoxia-inducible factor-1α
metabolic reprogramming
Journal
Cancer science
ISSN: 1349-7006
Titre abrégé: Cancer Sci
Pays: England
ID NLM: 101168776
Informations de publication
Date de publication:
Aug 2020
Aug 2020
Historique:
received:
27
12
2019
revised:
30
05
2020
accepted:
08
06
2020
pubmed:
13
6
2020
medline:
15
12
2020
entrez:
13
6
2020
Statut:
ppublish
Résumé
Recent studies have revealed that metabolic reprogramming is closely associated with epithelial-mesenchymal transition (EMT) during cancer progression. Aldolase A (ALDOA) is a key glycolytic enzyme that is highly expressed in several types of cancer. In this study, we found that ALDOA is highly expressed in uterine cervical adenocarcinoma and that high ALDOA expression promotes EMT to increase malignant potentials, such as metastasis and invasiveness, in cervical adenocarcinoma cells. In human surgical specimens, ALDOA was highly expressed in cervical adenocarcinoma and high ALDOA expression was correlated with lymph node metastasis, lymphovascular infiltration, and short overall survival. Suppression of ALDOA expression significantly reduced cell growth, migration, and invasiveness of cervical cancer cells. Aldolase A expression was partially regulated by hypoxia-inducible factor-1α (HIF-1α). Shotgun proteome analysis revealed that cell-cell adhesion-related proteins were significantly increased in ALDOA-overexpressing cells. Interestingly, overexpression of ALDOA caused severe morphological changes, including a cuboidal-to-spindle shape shift and reduced microvilli formation, coincident with modulation of the expression of typical EMT-related proteins. Overexpression of ALDOA increased migration and invasion in vitro. Furthermore, overexpression of ALDOA induced HIF-1α, suggesting a positive feedback loop between ALDOA and HIF-1α. In conclusion, ALDOA is overexpressed in cervical adenocarcinoma and contributes to malignant potentials of tumor cells through modulation of HIF-1α signaling. The feedback loop between ALDOA and HIF-1α could become a therapeutic target to improve the prognosis of this malignancy.
Identifiants
pubmed: 32530543
doi: 10.1111/cas.14524
pmc: PMC7419050
doi:
Substances chimiques
HIF1A protein, human
0
Hypoxia-Inducible Factor 1, alpha Subunit
0
RNA, Small Interfering
0
ALDOA protein, human
EC 4.1.2.13
Fructose-Bisphosphate Aldolase
EC 4.1.2.13
Types de publication
Journal Article
Observational Study
Langues
eng
Sous-ensembles de citation
IM
Pagination
3071-3081Subventions
Organisme : The Suhara Foundation
Organisme : Japan Society for the Promotion of Science
ID : JP17K08697
Organisme : Japan Society for the Promotion of Science
ID : JP17K08698
Organisme : Japan Society for the Promotion of Science
ID : JP18K15084
Organisme : Japan Society for the Promotion of Science
ID : JP19K16561
Informations de copyright
© 2020 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.
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