天津总医院+南开大学:白杨素或可抑制大肠癌
创作:Lexi 审核:Lexi 2020年10月19日
  • 结直肠癌(CRC)细胞发生上皮-间充质转化(EMT)时,软骨寡聚基质蛋白(COMP)与肌动蛋白结合转胶蛋白(TAGLN)互作,参与细胞骨架重塑并促进恶性进展;
  • COMP在恶性CRC中高表达,与TAGLN表达呈正相关;
  • COMP低表达抑制CRC转移和侵袭,过表达促进EMT;
  • 高通量分子对接虚拟筛选结果发现,白杨素(从矢车菊中提取的黄酮类化合物)可根据结构靶向COMP/TAGLN复合物;
  • 白杨素可在体内外抑制CRC EMT、诱导癌细胞凋亡,并抑制CRC恶性进展。
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Lexi
天津医科大学总医院的王邦茂和曹海龙、南开大学的孙涛和杨诚与团队发表在Theranostics的研究发现,软骨寡聚基质蛋白(COMP)可与肌动蛋白结合转胶蛋白(TAGLN)互作,促进结直肠癌(CRC)细胞发生上皮-间充质转化(EMT)。通过对传统中药数据库进行高通量分子对接虚拟筛选,发现白杨素可靶向COMP/TAGLN复合物,并可在体内外抑制CRC细胞生长和EMT。
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Theranostics [IF:11.556]

Cartilage Oligomeric Matrix Protein promotes epithelial-mesenchymal transition by interacting with Transgelin in Colorectal Cancer

结直肠癌中软骨寡聚基质蛋白通过与转胶蛋白的相互作用促进上皮-间充质转化

10.7150/thno.44456

2020-07-09, Article

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Background and Purpose: The role of the cartilage oligomeric matrix protein (COMP) in epithelial-mesenchymal transition (EMT) in tumor progression has been studied, but its exact regulatory mechanism remains unknown.
Methods: The interaction between COMP and the actin-binding protein transgelin (TAGLN) was identified by interaction protein prediction and co-immunoprecipitation and verified through the stochastic optical reconstruction microscopy (STORM) and duolink experiments. Western blot and immunofluorescence analyses were conducted to detect the changes in EMT-related markers after COMP overexpression and knockdown. Molecular docking and Biacore of the interaction interface of COMP/TAGLN revealed that Chrysin directly targeted COMP. The promotion of COMP and the Chrysin inhibition of EMT were detected through the cell migration, invasion, apoptosis, and xenotransplantation of nude mice.
Results: COMP interacts with TAGLN in EMT in colorectal cancer to regulate cytoskeletal remodeling and promote malignant progression. COMP is highly expressed in highly malignant colorectal cancer and positively correlated with TAGLN expression. COMP knockdown can inhibit colorectal cancer metastasis and invasion, whereas COMP overexpression promotes EMT in colorectal cancer. Through virtual screening of the protein interaction interface, Chrysin, a flavonoid compound extracted from Oroxylum indicum, was found to have the highest docking score to the COMP/TAGLN complex. Chrysin inhibited COMP, thereby preventing EMT and the malignant progression of colorectal cancer.
Conclusions: This study illustrated the role of COMP in EMT and suggested that COMP/TAGLN may be a potential tumor therapeutic target. Chrysin exhibits obvious antitumor effects. This work provides a preliminary antitumor therapy to target COMP or its interaction protein to inhibit EMT.

First Authors:
Weilong Zhong,Huiqin Hou

Correspondence Authors:
Cheng Yang,Tao Sun,Hailong Cao,Bangmao Wang

All Authors:
Weilong Zhong,Huiqin Hou,Tianyu Liu,Shuai Su,Xiaonan Xi,Yusheng Liao,Runxiang Xie,Ge Jin,Xiang Liu,Lanping Zhu,Hongxia Zhang,Xueli Song,Cheng Yang,Tao Sun,Hailong Cao,Bangmao Wang

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