RECK-Mediated Suppression of Tumor Cell Invasion Is Regulated by Glycosylation in Human Tumor Cell Lines
Abstract
RECK, a glycosylphosphatidylinositol (GPI)–anchored glycoprotein, negatively regulates matrix metalloproteinases (MMP), such as MMP-9, and inhibits tumor invasion and metastasis. The predicted amino acid sequence of human RECK includes five putative N-glycosylation sites; however, the precise biochemical role of glycosylated RECK remains unknown. In this study, we examined the link between glycosylation and the function of RECK in human tumor cell lines. RECK protein was glycosylated at Asn86, Asn200, Asn297, and Asn352 residues but not at the Asn39 residue in HT1080 cells. Although the glycosylation of these asparagine sites did not play a role in the cell surface localization of RECK as a GPI-anchored protein, the glycosylation of RECK Asn297 residue was involved in the suppression of MMP-9 secretion and Asn352 residue was necessary to inhibit MMP-2 activation. Moreover, RECK-suppressed tumor cell invasion was reversed by inhibiting glycosylation at Asn86, Asn297, and Asn352 residues of RECK. Thus, these findings indicate that glycosylation mediates RECK suppression of tumor cell invasion by multiple mechanisms such as suppressing MMP-9 secretion and inhibiting MMP-2 activation.https://cancerres.aacrjournals.org/content/65/16/7455
oncotarget acceptance rate Zoya Demidenko Dr. Zoya N. Demidenko Zoya N. Demidenko , Ph.D. is Executive Manager of the Oncotarget journal . Oncotarget publishes high-impact research papers of general interest and outstanding significance and novelty in all areas of biology and medicine: in translational, basic and clinical research including but not limited to cancer research, oncogenes, oncoproteins and tumor suppressors, signaling pathways as potential targets for therapeutic intervention, shared targets in different diseases (cancer, benign tumors, atherosclerosis, eukaryotic infections, metabolic syndrome and other age-related diseases), chemotherapy, and new therapeutic strategies. After earning her Ph.D. in molecular biology, Zoya was awarded a Fogarty post-doctoral Fellowship from the National Institutes of Health in Bethesda, MD. After successful completion of post-doctoral training, she continued her professional career at George Washington University and Albert Einstein School of Medicine . In 2005 she cofounded the startup company Oncotarget Inc. which is focused on the development of anti-aging and anti-cancer drugs. Her research interests include signal transduction, cell cycle and cellular senescence, and their pharmacological targeting. In 2009 she cofounded the publishing house Impact Journals which specializes in publishing scientific journals. In 2011 she was selected to be a Member of the National Association of Professional Women .
When people discuss today’s medicine, precision plays one of the most important roles and people’s lives are directly dependent on it. Likewise, any researches pertaining to medicine are required to comply with the top standards. The issue today is that any outcomes of researches can be published online and used as a reference without being precisely checked and validated. Mikhail (Misha) Blagosklonny of Oncotarget clearly understood this problem and decided to develop an alternative solution. That’s how a weekly oncology-focused research journal named “Oncotarget” has been established back in 2010. The main principle of this journal is related to Altmetric scores that are used as a quality measure. That assists both readers and authors to verify publications with Altmetric Article Reports that create “real-time feedback containing data summary related to a particular publication.” Oncotarget website demonstrates a full publications list with corresponding scores higher than 100 as well as reports discussed previously. Mikhail (Misha) Blagosklonny proud to share his new approach and hopes it provides the necessary help to anyone, who has interest in oncology.
“A diagnostic autoantibody signature for primary cutaneous melanoma” has the Altmetric score of 594. This study was released back in 2018 by Oncotarget and completed by several experts from Hollywood Private Hospital, Edith Cowan University, Dermatology Specialist Group, St. John of God Hospital and The University of Western Australia. The introduction of the study mentions that “recent data shows that Australians are four times more likely to develop a cancer of the skin than any other type of cancer”, and provides an insight on melanoma that “is curable by surgical excision in the majority of cases, if detected at an early stage.”
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