Analysis of the effect of increased ¿2,3-sialylation on RTK activation in MKN45 gastric cancer spheroids treated with crizotinib

• Type: Article in International Scientific Journal
• Date: 2020

Authors

Balmaña, M (Author) Other; Diniz, F (Author) Other; Feijão, T (Author) Other; Barrias, CC (Author) Other; Mereiter, S (Author) Other; Celso Reis (Author) ICBAS

Journal

Title: International Journal Of Molecular Sciences

Vol. 21 No. 7

Final page: 722

ISSN: 1661-6596

Publisher: MDPI

Indexing

ISI Web of Knowledge - 6 Citations

Scopus - 4 Citations

Other information

Authenticus ID: P-00R-NC7

DOI: 10.3390/ijms21030722

Abstract (EN): In the scenario of personalized medicine, targeted therapies are currently the focus of cancer drug development. These drugs can block the growth and spread of tumor cells by interfering with key molecules involved in malignancy, such as receptor tyrosine kinases (RTKs). MET and Recepteur d¿Origine Nantais (RON), which are RTKs frequently overactivated in gastric cancer, are glycoprotein receptors whose activation have been shown to be modulated by the cellular glycosylation. In this work, we address the role of sialylation in gastric cancer therapy using an innovative 3D high-throughput cell culture methodology that mimics better the in vivo tumor features. We evaluate the response to targeted treatment of glycoengineered gastric cancer cell models overexpressing the sialyltransferases ST3GAL4 or ST3GAL6 by subjecting 3D spheroids to the tyrosine kinase inhibitor crizotinib. We show here that 3D spheroids of ST3GAL4 or ST3GAL6 overexpressing MKN45 gastric cancer cells are less affected by the inhibitor. In addition, we disclose a potential compensatory pathway via activation of the Insulin Receptor upon crizotinib treatment. Our results suggest that cell sialylation, in addition of being involved in tumor progression, could play a critical role in the response to tyrosine kinase inhibitors in gastric cancer. © 2020 by the authors. Licensee MDPI, Basel, Switzerland.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 16