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Verfasst von:López-Cortés, Andrés [VerfasserIn]   i
 Prathap, Lavanya [VerfasserIn]   i
 Ortiz-Prado, Esteban [VerfasserIn]   i
 Kyriakidis, Nikolaos C. [VerfasserIn]   i
 León Cáceres, Ángela [VerfasserIn]   i
 Armendáriz-Castillo, Isaac [VerfasserIn]   i
 Vera-Guapi, Antonella [VerfasserIn]   i
 Yumiceba, Verónica [VerfasserIn]   i
 Simbaña-Rivera, Katherine [VerfasserIn]   i
 Echeverría-Garcés, Gabriela [VerfasserIn]   i
 García-Cárdenas, Jennyfer M. [VerfasserIn]   i
 Pérez-Villa, Andy [VerfasserIn]   i
 Guevara-Ramírez, Patricia [VerfasserIn]   i
 Abad-Sojos, Andrea [VerfasserIn]   i
 Bautista, Jhommara [VerfasserIn]   i
 Puig San Andrés, Lourdes [VerfasserIn]   i
 Varela, Nelson [VerfasserIn]   i
 Guerrero, Santiago [VerfasserIn]   i
Titel:The close interaction between hypoxia-related proteins and metastasis in pancarcinomas
Verf.angabe:Andrés López-Cortés, Lavanya Prathap, Esteban Ortiz-Prado, Nikolaos C. Kyriakidis, Ángela León Cáceres, Isaac Armendáriz-Castillo, Antonella Vera-Guapi, Verónica Yumiceba, Katherine Simbaña-Rivera, Gabriela Echeverría-Garcés, Jennyfer M. García-Cárdenas, Andy Pérez-Villa, Patricia Guevara-Ramírez, Andrea Abad-Sojos, Jhommara Bautista, Lourdes Puig San Andrés, Nelson Varela & Santiago Guerrero
E-Jahr:2022
Jahr:30 June 2022
Umfang:17 S.
Fussnoten:Gesehen am 30.01.2023
Titel Quelle:Enthalten in: Scientific reports
Ort Quelle:[London] : Macmillan Publishers Limited, part of Springer Nature, 2011
Jahr Quelle:2022
Band/Heft Quelle:12(2022), Artikel-ID 11100, Seite 1-17
ISSN Quelle:2045-2322
Abstract:Many primary-tumor subregions exhibit low levels of molecular oxygen and restricted access to nutrients due to poor vascularization in the tissue, phenomenon known as hypoxia. Hypoxic tumors are able to regulate the expression of certain genes and signaling molecules in the microenvironment that shift it towards a more aggressive phenotype. The transcriptional landscape of the tumor favors malignant transformation of neighboring cells and their migration to distant sites. Herein, we focused on identifying key proteins that participate in the signaling crossroads between hypoxic environment and metastasis progression that remain poorly defined. To shed light on these mechanisms, we performed an integrated multi-omics analysis encompassing genomic/transcriptomic alterations of hypoxia-related genes and Buffa hypoxia scores across 17 pancarcinomas taken from the PanCancer Atlas project from The Cancer Genome Atlas consortium, protein-protein interactome network, shortest paths from hypoxia-related proteins to metastatic and angiogenic phenotypes, and drugs involved in current clinical trials to treat the metastatic disease. As results, we identified 30 hypoxia-related proteins highly involved in metastasis and angiogenesis. This set of proteins, validated with the MSK-MET Project, could represent key targets for developing therapies. The upregulation of mRNA was the most prevalent alteration in all cancer types. The highest frequencies of genomic/transcriptomic alterations and hypoxia score belonged to tumor stage 4 and positive metastatic status in all pancarcinomas. The most significantly associated signaling pathways were HIF-1, PI3K-Akt, thyroid hormone, ErbB, FoxO, mTOR, insulin, MAPK, Ras, AMPK, and VEGF. The interactome network revealed high-confidence interactions among hypoxic and metastatic proteins. The analysis of shortest paths revealed several ways to spread metastasis and angiogenesis from hypoxic proteins. Lastly, we identified 23 drugs enrolled in clinical trials focused on metastatic disease treatment. Six of them were involved in advanced-stage clinical trials: aflibercept, bevacizumab, cetuximab, erlotinib, ipatasertib, and panitumumab.
DOI:doi:10.1038/s41598-022-15246-y
URL:Bitte beachten Sie: Dies ist ein Bibliographieeintrag. Ein Volltextzugriff für Mitglieder der Universität besteht hier nur, falls für die entsprechende Zeitschrift/den entsprechenden Sammelband ein Abonnement besteht oder es sich um einen OpenAccess-Titel handelt.

Volltext: https://doi.org/10.1038/s41598-022-15246-y
 Volltext: https://www.nature.com/articles/s41598-022-15246-y
 DOI: https://doi.org/10.1038/s41598-022-15246-y
Datenträger:Online-Ressource
Sprache:eng
Sach-SW:Cancer
 Metastasis
 Molecular medicine
K10plus-PPN:1832648427
Verknüpfungen:→ Zeitschrift

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