دورية أكاديمية
Aspartate β-Hydroxylase Is Upregulated in Head and Neck Squamous Cell Carcinoma and Regulates Invasiveness in Cancer Cell Models
| العنوان: | Aspartate β-Hydroxylase Is Upregulated in Head and Neck Squamous Cell Carcinoma and Regulates Invasiveness in Cancer Cell Models |
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| المؤلفون: | Pritha Mukherjee, Xin Zhou, Susana Galli, Bruce Davidson, Lihua Zhang, Jaeil Ahn, Reem Aljuhani, Julius Benicky, Laurie Ailles, Vitor H. Pomin, Mark Olsen, Radoslav Goldman |
| المصدر: | International Journal of Molecular Sciences, Vol 25, Iss 9, p 4998 (2024) |
| بيانات النشر: | MDPI AG, 2024. |
| سنة النشر: | 2024 |
| المجموعة: | LCC:Biology (General) LCC:Chemistry |
| مصطلحات موضوعية: | HNSCC, aspartate β-hydroxylase (ASPH), heparan 6-O-endosulfatase 2 (SULF2), MO-I-1151, HfFucCS, primary head and neck CAF, Biology (General), QH301-705.5, Chemistry, QD1-999 |
| الوصف: | Aspartate β-hydroxylase (ASPH) is a protein associated with malignancy in a wide range of tumors. We hypothesize that inhibition of ASPH activity could have anti-tumor properties in patients with head and neck cancer. In this study, we screened tumor tissues of 155 head and neck squamous cell carcinoma (HNSCC) patients for the expression of ASPH using immunohistochemistry. We used an ASPH inhibitor, MO-I-1151, known to inhibit the catalytic activity of ASPH in the endoplasmic reticulum, to show its inhibitory effect on the migration of SCC35 head and neck cancer cells in cell monolayers and in matrix-embedded spheroid co-cultures with primary cancer-associated fibroblast (CAF) CAF 61137 of head and neck origin. We also studied a combined effect of MO-I-1151 and HfFucCS, an inhibitor of invasion-blocking heparan 6-O-endosulfatase activity. We found ASPH was upregulated in HNSCC tumors compared to the adjacent normal tissues. ASPH was uniformly high in expression, irrespective of tumor stage. High expression of ASPH in tumors led us to consider it as a therapeutic target in cell line models. ASPH inhibitor MO-I-1151 had significant effects on reducing migration and invasion of head and neck cancer cells, both in monolayers and matrix-embedded spheroids. The combination of the two enzyme inhibitors showed an additive effect on restricting invasion in the HNSCC cell monolayers and in the CAF-containing co-culture spheroids. We identify ASPH as an abundant protein in HNSCC tumors. Targeting ASPH with inhibitor MO-I-1151 effectively reduces CAF-mediated cellular invasion in cancer cell models. We propose that the additive effect of MO-I-1151 with HfFucCS, an inhibitor of heparan 6-O-endosulfatases, on HNSCC cells could improve interventions and needs to be further explored. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 25094998 1422-0067 1661-6596 |
| العلاقة: | https://www.mdpi.com/1422-0067/25/9/4998Test; https://doaj.org/toc/1661-6596Test; https://doaj.org/toc/1422-0067Test |
| DOI: | 10.3390/ijms25094998 |
| الوصول الحر: | https://doaj.org/article/6d1b9848fe6f4ab58bf0b8b5a3da28eaTest |
| رقم الانضمام: | edsdoj.6d1b9848fe6f4ab58bf0b8b5a3da28ea |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 25094998 14220067 16616596 |
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| DOI: | 10.3390/ijms25094998 |