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Formin-like 2 promotes angiogenesis and metastasis of colorectal cancer by regulating the EGFL6/CKAP4/ERK axis |
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| Authors: | Guoyang He Wei Li Wenli Zhao Hui Men Qingqing Chen Jinlong Hu Jingyu Zhang Huifang Zhu Wenxin Wang Meijing Deng Zishan Xu Gaoxiang Wang Lin Zhou Xinlai Qian Li Liang |
| Institution: | 1. Department of Pathology, Xinxiang Medical University, Xinxiang, China;2. School of Forensic Medicine, Xinxiang Medical University, Xinxiang, China;3. Department of Pathology, Haikou Affiliated Hospital of Central South University Xiangya School of Medicine, Haikou, China
Department of Pathology, Southern Medical University, Guangzhou, China;4. Department of Pathology, Sun Yat-sen University Cancer Center, Guangzhou, China State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China;5. Department of Colorectal and Anal Surgery, First Affiliated Hospital of Xinxiang Medical University, Xinxiang, China;6. Department of Breast and Thyroid Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China;7. Department of Pathology, Xinxiang Medical University, Xinxiang, China Department of Pathology, Third Affiliated Hospital of Xinxiang Medical University, Xinxiang, China;8. Department of Pathology, Southern Medical University, Guangzhou, China |
| Abstract: | Increasing evidence indicates that angiogenesis plays a pivotal role in tumor progression. Formin-like 2 (FMNL2) is well-known for promoting metastasis; however, the molecular mechanisms by which FMNL2 promotes angiogenesis in colorectal cancer (CRC) remain unclear. Here, we found that FMNL2 promotes angiogenesis and metastasis of CRC in vitro and in vivo. The GDB/FH3 domain of FMNL2 directly interacts with epidermal growth factor-like protein 6 (EGFL6). Formin-like 2 promotes EGFL6 paracrine signaling by exosomes to regulate angiogenesis in CRC. Cytoskeleton associated protein 4 (CKAP4) is a downstream target of EGFL6 and is involved in CRC angiogenesis. Epidermal growth factor-like protein 6 binds to the N-terminus of CKAP4 to promote the migration of HUVECs by activating the ERK/MMP pathway. These findings suggest that FMNL2 promotes the migration of HUVECs and enhances angiogenesis and tumorigenesis in CRC by regulating the EGFL6/CKAP4/ERK axis. Therefore, the EGFL6/CKAP4/ERK axis could be a candidate therapeutic target for CRC treatment. |
| Keywords: | angiogenesis CKAP4 colorectal cancer EGFL6 FMNL2 |