دورية أكاديمية
Modulation of Autophagy Direction to Enhance Antitumor Effect of Endoplasmic‐Reticulum‐Targeted Therapy: Left or Right?
العنوان: | Modulation of Autophagy Direction to Enhance Antitumor Effect of Endoplasmic‐Reticulum‐Targeted Therapy: Left or Right? |
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المؤلفون: | Xinran Shen, Yudi Deng, Liqiang Chen, Chendong Liu, Lian Li, Yuan Huang |
المصدر: | Advanced Science, Vol 10, Iss 23, Pp n/a-n/a (2023) |
بيانات النشر: | Wiley, 2023. |
سنة النشر: | 2023 |
المجموعة: | LCC:Science |
مصطلحات موضوعية: | antimetastasis therapy, autophagy modulation, drug delivery system, endoplasmic reticulum targeting, immunotherapy, Science |
الوصف: | Abstract Strategies that induce dysfunction in the endoplasmic reticulum (ER) hold great promise for anticancer therapy, but remain unsatisfactory due to the compensatory autophagy induction after ER disruption. Moreover, as autophagy can either promote or suppress cell survival, which direction of autophagy better suits ER‐targeting therapy remains controversial. Here, a targeted nanosystem is constructed, which efficiently escorts anticancer therapeutics into the ER, triggering substantial ER stress and autophagy. Concurrently, an autophagy enhancer or inhibitor is combined into the same nanoparticle, and their impacts on ER‐related activities are compared. In the orthotopic breast cancer mouse model, the autophagy enhancer increases the antimetastasis effect of ER‐targeting therapy and suppresses over 90% of cancer metastasis, while the autophagy inhibitor has a bare effect. Mechanism studies reveal that further enhancing autophagy accelerates central protein snail family transcriptional repressor 1 (SNAI1) degradation, suppressing downstream epithelial–mesenchymal transition, while inhibiting autophagy does the opposite. With the same trend, ER‐targeting therapy combined with an autophagy enhancer provokes stronger immune response and tumor inhibition than the autophagy inhibitor. Mechanism studies reveal that the autophagy enhancer elevates Ca2+ release from the ER and functions as a cascade amplifier of ER dysfunction, which accelerates Ca2+ release, resulting in immunogenic cell death (ICD) induction and eventually triggering immune responses. Together, ER‐targeting therapy benefits from the autophagy‐enhancing strategy more than the autophagy‐inhibiting strategy for antitumor and antimetastasis treatment. |
نوع الوثيقة: | article |
وصف الملف: | electronic resource |
اللغة: | English |
تدمد: | 2198-3844 |
العلاقة: | https://doaj.org/toc/2198-3844Test |
DOI: | 10.1002/advs.202301434 |
الوصول الحر: | https://doaj.org/article/8d4962b118104c1ba59cd6b52d611472Test |
رقم الانضمام: | edsdoj.8d4962b118104c1ba59cd6b52d611472 |
قاعدة البيانات: | Directory of Open Access Journals |
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