Upregulation of CD36, a Fatty Acid Translocase, Promotes Colorectal Cancer Metastasis by Increasing MMP28 and Decreasing E-Cadherin Expression
| العنوان: | Upregulation of CD36, a Fatty Acid Translocase, Promotes Colorectal Cancer Metastasis by Increasing MMP28 and Decreasing E-Cadherin Expression |
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| المؤلفون: | James Drury, Piotr G. Rychahou, Courtney O. Kelson, Mariah E. Geisen, Yuanyuan Wu, Daheng He, Chi Wang, Eun Y. Lee, B. Mark Evers, Yekaterina Y. Zaytseva |
| المصدر: | Cancers Cancers; Volume 14; Issue 1; Pages: 252 Cancers, Vol 14, Iss 252, p 252 (2022) |
| بيانات النشر: | MDPI, 2022. |
| سنة النشر: | 2022 |
| مصطلحات موضوعية: | Cancer Research, MMP28, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, E-cadherin, hemic and immune systems, colorectal cancer, digestive system diseases, metastasis, fatty-acid metabolism, CD36, Article, Oncology, parasitic diseases, RC254-282, circulatory and respiratory physiology |
| الوصف: | Simple Summary Colorectal cancer is the second leading cause of cancer-related death in the world. Upregulation of fatty acid metabolism is a hallmark of cancer and recent studies demonstrate that blocking fatty acid uptake is a promising therapeutic strategy. We have previously shown that CD36, a transporter of fatty acid, promotes colorectal cancer tumor growth. We have also demonstrated that high expression of CD36 is associated with cancer cells that are prone to metastasis. Here, in studying the role of CD36 in colorectal cancer, we found that CD36 promotes colorectal cancer invasion in vitro and metastasis in vivo and that overexpression of CD36 upregulates expression of the matrix metalloproteinase MMP28. Our data demonstrates that MMP28 cleaves and decreases expression of E-cadherin, a marker for epithelial-to-mesenchymal transition in colorectal cancers. This newly defined CD36–MMP28–E-cadherin axis provides new therapeutic targets for the treatment of colorectal cancer. Abstract Altered fatty acid metabolism continues to be an attractive target for therapeutic intervention in cancer. We previously found that colorectal cancer (CRC) cells with a higher metastatic potential express a higher level of fatty acid translocase (CD36). However, the role of CD36 in CRC metastasis has not been studied. Here, we demonstrate that high expression of CD36 promotes invasion of CRC cells. Consistently, CD36 promoted lung metastasis in the tail vein model and GI metastasis in the cecum injection model. RNA-Seq analysis of CRC cells with altered expression of CD36 revealed an association between high expression of CD36 and upregulation of MMP28, a novel member of the metallopeptidase family of proteins. Using shRNA-mediated knockdown and overexpression of CD36, we confirmed that CD36 regulates MMP28 expression in CRC cells. siRNA-mediated knockdown of MMP28 decreases invasion of CRC cells, suggesting that MMP28 regulates the metastatic properties of cells downstream of CD36. Importantly, high expression of MMP28 leads to a significant decrease in active E-cadherin and an increase in the products of E-cadherin cleavage, CTF1 and CTF2. In summary, upregulation of CD36 expression promotes the metastatic properties of CRC via upregulation of MMP28 and an increase in E-cadherin cleavage, suggesting that targeting the CD36–MMP28 axis may be an effective therapeutic strategy for CRC metastasis. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 2072-6694 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::9fe0f543fe8c7c9e332cac4077f5505fTest http://europepmc.org/articles/PMC8750155Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....9fe0f543fe8c7c9e332cac4077f5505f |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 20726694 |
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