Academic Journal

Integrin α6β4 Confers Doxorubicin Resistance in Cancer Cells by Suppressing Caspase-3–Mediated Apoptosis: Involvement of N-Glycans on β4 Integrin Subunit

التفاصيل البيبلوغرافية
العنوان: Integrin α6β4 Confers Doxorubicin Resistance in Cancer Cells by Suppressing Caspase-3–Mediated Apoptosis: Involvement of N-Glycans on β4 Integrin Subunit
المؤلفون: Yoshinobu Kariya, Jianguo Gu, Yukiko Kariya
المصدر: Biomolecules, Vol 13, Iss 12, p 1752 (2023)
بيانات النشر: MDPI AG, 2023.
سنة النشر: 2023
المجموعة: LCC:Microbiology
مصطلحات موضوعية: α6β4 integrin, doxorubicin, chemoresistance, caspase-3, N-acetylglucosaminyltransferase III (GnT-III), bisecting GlcNAc, Microbiology, QR1-502
الوصف: Drug resistance is a major obstacle to successful cancer treatment. Therefore, it is essential to understand the molecular mechanisms underlying drug resistance to develop successful therapeutic strategies. α6β4 integrin confers resistance to apoptosis and regulates the survival of cancer cells; however, it remains unclear whether α6β4 integrin is directly involved in chemoresistance. Here, we show that α6β4 integrin promotes doxorubicin resistance by decreasing caspase-3–mediated apoptosis. We found that the overexpression of α6β4 integrin by the β4 integrin gene rendered MDA-MB435S and Panc-1 cells more resistant to doxorubicin than control cells. The acquired resistance to doxorubicin by α6β4 integrin expression was abolished by the deletion of the cytoplasmic signal domain in β4 integrin. Similar results were found in MDA-MB435S and Panc-1 cells when N-glycan-defective β4 integrin mutants were overexpressed or bisecting GlcNAc residues were increased on β4 integrin by the co-expression of N-acetylglucosaminyltransferase III with β4 integrin. The abrogation of α6β4 integrin-mediated resistance to doxorubicin was accompanied by reduced cell viability and an increased caspase-3 activation. Taken together, our results clearly suggest that α6β4 integrin signaling plays a key role in the doxorubicin resistance of cancer cells, and N-glycans on β4 integrin are involved in the regulation of cancer cells.
نوع الوثيقة: article
وصف الملف: electronic resource
اللغة: English
تدمد: 2218-273X
Relation: https://www.mdpi.com/2218-273X/13/12/1752; https://doaj.org/toc/2218-273X
DOI: 10.3390/biom13121752
URL الوصول: https://doaj.org/article/57208de81f9045238e71e8b04efe69e9
رقم الانضمام: edsdoj.57208de81f9045238e71e8b04efe69e9
قاعدة البيانات: Directory of Open Access Journals
الوصف
تدمد:2218273X
DOI:10.3390/biom13121752