Affiliation:
1. UMR INSERM 1308 CAPTuR, Faculty of Medicine, University of Limoges, 2 street of Dr. Raymond Marcland, 87025 Limoges CEDEX-France
2. IGBMC - Proteomic platform, 1 street of Laurent Fries, BP 10142, 67404 Illkirch CEDEX
Abstract
Abstract
Sortilin, a glycoprotein belonging to the Vps10 family, is mainly recognized for its contribution to protein sorting. Its dichotomous role in oncology, between tumor promotion and suppression, remains highly controversial. Our present study reveals a novel mechanism relying on the nuclear localization of sortilin, acting on transcription, chromatin reorganization and DNA repair. Its role in limiting tumor progression of lung adenocarcinoma cell lines was confirmed with sustained EGFR proliferative signaling. Furthermore, we report that sortilin overexpression limits the growth of NCI-H1975 and NCI-H3255 cell lines, regulating gene expression but also indirectly altering oncogenic pathways such as MTOR and AKT. Through its transcriptional action, sortilin interacts directly with proteins central to DNA repair mechanisms and chromatin reorganization. Finally, our findings reshape the traditional view of sortilin, suggesting implications not restricted to its simple protein transport, which contributes to explain its heterogeneous roles in different tumors. These insights also position sortilin as a promising candidate to engineer innovative therapeutics in lung adenocarcinoma.
Publisher
Research Square Platform LLC
Reference27 articles.
1. Tumor co-expression of progranulin and sortilin as a prognostic biomarker in breast cancer;Berger K;BMC Cancer,2021
2. Sortilin May Be a Potential Therapeutic Target in Pancreatic Cancer - The ASCO Post. https://ascopost.com/news/august-2020/sortilin-may-be-a-potential-therapeutic-target-in-pancreatic-cancer/.
3. Sortilin is associated with breast cancer aggressiveness and contributes to tumor cell adhesion and invasion;Roselli S;Oncotarget,2015
4. Fine-tuning roles of endogenous brain-derived neurotrophic factor, TrkB and sortilin in colorectal cancer cell survival;Akil H;PloS One,2011
5. Sortilin as a Novel Diagnostic and Therapeutic Biomarker in Chronic Lymphocytic Leukemia;Farahi L;Avicenna J. Med. Biotechnol.,2019