التفاصيل البيبلوغرافية
| العنوان: |
Extracellular Matrix Sulfation in the Tumor Microenvironment Stimulates Cancer Stemness and Invasiveness |
| المؤلفون: |
Alican Kuşoğlu, Deniz Örnek, Aslı Dansık, Ceren Uzun, Sena Nur Özkan, Sevgi Sarıca, Kardelen Yangın, Şevval Özdinç, Duygu Turan Sorhun, Nuriye Solcan, Efe Can Doğanalp, Øystein Arlov, Katherine Cunningham, Ismail C. Karaoğlu, Seda Kizilel, Ihsan Solaroğlu, Pınar Bulutay, Pınar Fırat, Suat Erus, Serhan Tanju, Şükrü Dilege, Gordana Vunjak‐Novakovic, Nurcan Tuncbag, Ece Öztürk |
| المصدر: |
Advanced Science, Vol 11, Iss 36, Pp n/a-n/a (2024) |
| بيانات النشر: |
Wiley, 2024. |
| سنة النشر: |
2024 |
| المجموعة: |
LCC:Science |
| مصطلحات موضوعية: |
cancer, extracellular matrix (ECM), hydrogels, tissue engineering, tumor microenvironment (TME), tumor models, Science |
| الوصف: |
Abstract Tumor extracellular matrices (ECM) exhibit aberrant changes in composition and mechanics compared to normal tissues. Proteoglycans (PG) are vital regulators of cellular signaling in the ECM with the ability to modulate receptor tyrosine kinase (RTK) activation via their sulfated glycosaminoglycan (sGAG) side chains. However, their role on tumor cell behavior is controversial. Here, it is demonstrated that PGs are heavily expressed in lung adenocarcinoma (LUAD) patients in correlation with invasive phenotype and poor prognosis. A bioengineered human lung tumor model that recapitulates the increase of sGAGs in tumors in an organotypic matrix with independent control of stiffness, viscoelasticity, ligand density, and porosity, is developed. This model reveals that increased sulfation stimulates extensive proliferation, epithelial‐mesenchymal transition (EMT), and stemness in cancer cells. The focal adhesion kinase (FAK)‐phosphatidylinositol 3‐kinase (PI3K) signaling axis is identified as a mediator of sulfation‐induced molecular changes in cells upon activation of a distinct set of RTKs within tumor‐mimetic hydrogels. The study shows that the transcriptomic landscape of tumor cells in response to increased sulfation resembles native PG‐rich patient tumors by employing integrative omics and network modeling approaches. |
| نوع الوثيقة: |
article |
| وصف الملف: |
electronic resource |
| اللغة: |
English |
| تدمد: |
2198-3844 |
| Relation: |
https://doaj.org/toc/2198-3844 |
| DOI: |
10.1002/advs.202309966 |
| URL الوصول: |
https://doaj.org/article/a63380413b3f4842a13ba93e08720412 |
| رقم الانضمام: |
edsdoj.63380413b3f4842a13ba93e08720412 |
| قاعدة البيانات: |
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