دورية أكاديمية
A novel 2-pyrone derivative, BHP, impedes oncogenic KRAS-driven malignant progression in breast cancer
| العنوان: | A novel 2-pyrone derivative, BHP, impedes oncogenic KRAS-driven malignant progression in breast cancer |
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| المساهمون: | Rae-Kwon Kim, Yongjoon Suh, Eun-Jung Lim, Ki-Chun Yoo, Ga-Haeng Lee, Yan-Hong Cui, Arang Son, Eunji Hwang, Nizam Uddin, Joo-Mi Yi, Seok-Gu Kang, Su-Jae Lee, Kang, Seok Gu |
| سنة النشر: | 2013 |
| مصطلحات موضوعية: | Antineoplastic Agents/pharmacology, Breast Neoplasms/drug therapy, Breast Neoplasms/pathology, Cell Line, Tumor, Disease Progression, Epithelial-Mesenchymal Transition, Female, Humans, Neoplasm Invasiveness, Proto-Oncogene Proteins/antagonists & inhibitors, Proto-Oncogene Proteins p21(ras), Pyrones/pharmacology, ras Proteins/antagonists & inhibitors, Epithelial�뱈esenchymal transition, Invasion, Malignant progression, Migration, Ras signaling pathway, 慣-Pyrone derivative |
| الوصف: | Elevated KRAS expression has been frequently associated with cancer progression including breast cancer; however, therapeutic approaches targeting KRAS have been widely unsuccessful and KRAS mutant cancers remain unsolved problem in cancer therapy. In this study, we found that a new 2-pyrone derivative, 5-bromo-3-(3-hydroxyprop-1-ynyl)-2H-pyran-2-one (BHP) can block KRAS-driven breast cancer progression. Importantly, treatment with BHP effectively suppressed the migratory and invasive properties along with epithelial-mesenchymal transition (EMT) in MDA-MB231 breast cancer cells that carry oncogenic KRAS and mesenchymal malignant phenotypes. In parallel, BHP also sensitized the cells to anticancer treatment. Consistently, forced-expression of oncogenic KRAS bestowed the migratory and invasive properties, mesenchymal transition and resistance to anticancer treatment into normal human mammalian breast cells MCF10A and relatively non-malignant MCF7 and SK-BR3 breast cancer cells; however, treatment with BHP blocked those KRAS-induced malignant phenotypes. Notably, BHP interfered the interaction of KRAS with Raf-1 in concentration-dependent manner, thereby blocking the downstream effectors of KRAS signaling that is PI3K/AKT and ERK. Taken together, our findings indicate that the BHP, an 慣-pyrone derivative, suppresses malignant breast cancer progression by targeting of oncogenic KRAS signaling pathways. ; open |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | unknown |
| تدمد: | 0304-3835 1872-7980 |
| العلاقة: | CANCER LETTERS; J00448; OAK-2013-00943; https://ir.ymlib.yonsei.ac.kr/handle/22282913/87061Test; http://www.sciencedirect.com/science/article/pii/S0304383513004059Test; T201301848; CANCER LETTERS, Vol.337(1) : 49-57, 2013 |
| DOI: | 10.1016/j.canlet.2013.05.023 |
| الإتاحة: | https://doi.org/10.1016/j.canlet.2013.05.023Test https://ir.ymlib.yonsei.ac.kr/handle/22282913/87061Test http://www.sciencedirect.com/science/article/pii/S0304383513004059Test |
| حقوق: | CC BY-NC-ND 2.0 KR ; https://creativecommons.org/licenses/by-nc-nd/2.0/krTest/ ; not free |
| رقم الانضمام: | edsbas.4973FC13 |
| قاعدة البيانات: | BASE |
| تدمد: | 03043835 18727980 |
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| DOI: | 10.1016/j.canlet.2013.05.023 |