Research Papers:
Prohibitin, relocated to the front ends, can control the migration directionality of colorectal cancer cells
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Abstract
Li-Li Ma1,2,3,*, Lan Shen1,2,*, Gui-Hui Tong1,2,*, Na Tang4,*, Yang Luo5,*, Li-Li Guo1,2, Chun-Ting Hu6, Ying-Xin Huang1,2, Guan Huang1,2,7, Fang-Yan Jing8, Chao Liu9, Zhuo-Yi Li3, Na Zhou1,2, Qian-Wen Yan1,2, Yan Lei1,2, Shi-Jie Zhu1,2, Zhi-Qiang Cheng4, Guang-Wen Cao10, Yong-Jian Deng1,2 and Yan-Qing Ding1,2
1Department of Pathology, Nanfang Hospital and School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China
2Guangdong Provincial Key Laboratory of Molecular Tumor Pathology, Guangzhou 510515, China
3Department of Cardiothoracic Surgery, Taishan City People’s Hospital, Taishan 529200, China
4Department of Pathology, Shenzhen People’s Hospital, Second Clinical Medical College of Jinan University, Shenzhen 518020, China
5Department of Urinary Surgery, Nanfang Hospital and the Fifth Affiliated Hospital of Southern Medical University, Guangzhou 510900, China
6Pathology Center, Shanghai General Hospital Faculty of Basic Medicine, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
7Department of Pathology, Longgang District Central Hospital of Shenzhen, Shenzhen 518116, China
8Department of Anorectal Surgery, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China
9Department of Pathology and Laboratory Medicine, Guangdong General Hospital & Guangdong Academy of Medical Sciences, Guangzhou 510080, China
10Department of Epidemiology, Second Military Medical University, Shanghai 200433, China
*These authors have contributed equally to this work
Correspondence to:
Yong-Jian Deng, email: [email protected]
Yan-Qing Ding, email: [email protected]
Keywords: colorectal cancer, migration directionality, prohibitin, vascular endothelial growth factor, cell division cycle 42
Received: April 07, 2017 Accepted: June 20, 2017 Published: July 19, 2017
ABSTRACT
Directional migration is a cost-effective movement allowing invasion and metastatic spread of cancer cells. Although migration related to cytoskeletal assembly and microenvironmental chemotaxis has been elucidated, little is known about interaction between extracellular and intracellular molecules for controlling the migrational directionality. A polarized expression of prohibitin (PHB) in the front ends of CRC cells favors metastasis and is correlated with poor prognosis for 545 CRC patients. A high level of vascular endothelial growth factor (VEGF) in the interstitial tissue of CRC patients is associated with metastasis. VEGF bound to its receptor, neuropilin-1, can stimulate the activation of cell division cycle 42, which recruits intra-mitochondrial PHB to the front end of a CRC cell. This intracellular relocation of PHB results in the polymerization and reorganization of filament actin extending to the front end of the cell. As a result, the migration directionality of CRC cells is targeted towards VEGF. Together, these findings identify PHB as a key modulator of directional migration of CRC cells and a target for metastasis.
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