Εξειδίκευση τύπου :	Άρθρο σε επιστημονικό περιοδικό
Τίτλος:	Prox1 Suppresses the Proliferation of Breast Cancer Cells via Direct Inhibition of c-Myc Gene Expression
Δημιουργός/Συγγραφέας:	Michail, Artemis Gkikas, Dimitrios [EL] Στέλλας, Δημήτρης[EN] Stellas, Dimitris Kaltezioti, Valeria Politis, Panagiotis K
Ημερομηνία:	2023-07-17
Γλώσσα:	Αγγλικά
ISSN:	2073-4409
DOI:	10.3390/cells12141869
Άλλο:	37508533
Περίληψη:	Breast cancer is one of the most lethal malignancies in women worldwide and is characterized by rapid growth and low survival rates, despite advances in tumor biology and therapies. Novel therapeutic approaches require new insights into the molecular mechanisms of malignant transformation and progression. To this end, here, we identified Prox1 as a negative regulator of proliferation and tumor-related metabolism in breast cancer. In particular, we showed that breast tumors from human patients exhibited reduced levels of Prox1 expression, while high expression levels of Prox1 were associated with a favorable prognosis in breast cancer patients. Moreover, we experimentally demonstrated that Prox1 was sufficient to strongly suppress proliferation, migration, and the Warburg effect in human breast cancer cells without inducing apoptosis. Most importantly, over-expression of Prox1 inhibited breast tumor growth in vivo in both heterotopic and orthotopic xenograft mouse models. The anti-tumorigenic effect of Prox1 was mediated by the direct repression of c-Myc transcription and its downstream target genes. Consistently, c-Myc over-expression from an artificial promoter that was not targeted by Prox1 reversed Prox1's anti-tumor effects. These findings suggest that Prox1 has a tumor suppressive role via direct transcriptional regulation of c-Myc, making it a promising therapeutic gene for breast cancer.
Τίτλος πηγής δημοσίευσης:	Cells
Τόμος/Κεφάλαιο:	12
Τεύχος:	14
Θεματική Κατηγορία:	[EL] Βιοχημεία[EN] Biochemistry [EL] Νεοπλάσματα. Όγκοι. Ογκολογία (περ. Καρκίνος, κακινογόνες ουσίες)[EN] Neoplasms. Tumors. Oncology (Incl.cancer, carcinogens) [EL] Κυτταρολογία[EN] Cytology
Λέξεις-Κλειδιά:	MPC1 PDK1 Warburg effect Gene regulation Metabolism
EU Grant:	Fondation Sante Operational Program Competitiveness, Entrepreneurship and Innovation ERDF ΕΛ.ΙΔ.Ε.Κ
EU Grant identifier:	Politis-round2017 1782 T2EDK-02075
Κάτοχος πνευματικών δικαιωμάτων:	© 2023 by the authors. Licensee MDPI, Basel, Switzerland.
Όροι και προϋποθέσεις δικαιωμάτων:	This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/).
Ηλεκτρονική διεύθυνση στον εκδότη (link):	https://www.mdpi.com/2073-4409/12/14/1869
Εμφανίζεται στις συλλογές:	Ινστιτούτο Χημικής Βιολογίας - Επιστημονικό έργο