title: NHERF1 regulates the progression of colorectal cancer through the interplay with VEGFR2 pathway.
abstract: The oncogenic role of ectopic expression of Na+/H+ exchanger regulatory factor 1 (NHERF1) was recently suggested in colorectal cancer, where it was implicated in playing a role in the tumor hypoxia microenvironment. Here we showed that a high level expression of NHERF1 was found in colorectal cancer tissues and that the expression of NHERF1 was positively correlated with VEGFR2 expression. The prognostic value of VEGFR2 expression in colorectal cancer relied on the expression of NHERF1. The up-regulation of NHERF1 induced by the exposure to hypoxia in colon cancer cells depended on the activation of VEGFR2 signaling. NHERF1 in turn inhibited the activation of VEGFR2 signaling which could be regulated by the interaction between NHERF1 and VEGFR2, resulting in the reduction of migration and invasion of colon cancer cells. These results suggest a dynamic interplay between NHERF1 and VEGFR2 signaling in colorectal cancer, which could explain the contribution of NHERF1 to the regulation of tumor cell responses to the hypoxia microenvironment.
authors.affiliation: Department of Biochemistry and Molecular Biology, Capital Medical University, Beijing 100069, China.|Beijing Key Laboratory of Cancer & Metastasis Research, Capital Medical University, Beijing 100069, China.
authors.forename: Yanan
authors.initials: Y
authors.lastname: Gu
authors.affiliation: Department of Biochemistry and Molecular Biology, Capital Medical University, Beijing 100069, China.|Beijing Key Laboratory of Cancer & Metastasis Research, Capital Medical University, Beijing 100069, China.
authors.forename: Hefen
authors.initials: H
authors.lastname: Yu
authors.affiliation: Department of Biochemistry and Molecular Biology, Capital Medical University, Beijing 100069, China.|Beijing Key Laboratory of Cancer & Metastasis Research, Capital Medical University, Beijing 100069, China.
authors.forename: Chengcheng
authors.initials: C
authors.lastname: Hao
authors.affiliation: Beijing Key Laboratory of Cancer & Metastasis Research, Capital Medical University, Beijing 100069, China.|Cardiff China Medical Research Collaborative, Cardiff University School of Medicine, Heath Park, Cardiff CF14 4XN, UK.
authors.forename: Tracey A
authors.initials: TA
authors.lastname: Martin
authors.affiliation: Beijing Key Laboratory of Cancer & Metastasis Research, Capital Medical University, Beijing 100069, China.|Cardiff China Medical Research Collaborative, Cardiff University School of Medicine, Heath Park, Cardiff CF14 4XN, UK.
authors.forename: Rachel
authors.initials: R
authors.lastname: Hargest
authors.affiliation: Department of Biochemistry and Molecular Biology, Capital Medical University, Beijing 100069, China.|Beijing Key Laboratory of Cancer & Metastasis Research, Capital Medical University, Beijing 100069, China.
authors.forename: Junqi
authors.initials: J
authors.lastname: He
authors.affiliation: Department of Biochemistry and Molecular Biology, Capital Medical University, Beijing 100069, China.|Beijing Key Laboratory of Cancer & Metastasis Research, Capital Medical University, Beijing 100069, China.
authors.forename: Shan
authors.initials: S
authors.lastname: Cheng
authors.affiliation: Department of Biochemistry and Molecular Biology, Capital Medical University, Beijing 100069, China.|Beijing Key Laboratory of Cancer & Metastasis Research, Capital Medical University, Beijing 100069, China.|Cardiff China Medical Research Collaborative, Cardiff University School of Medicine, Heath Park, Cardiff CF14 4XN, UK.
authors.forename: Wen G
authors.initials: WG
authors.lastname: Jiang
mesh_terms: D045744:Cell Line, Tumor; D002465:Cell Movement; D015179:Colorectal Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D018450:Disease Progression; D025461:Feedback, Physiological; D006801:Humans; D009361:Neoplasm Invasiveness; D051966:Phospholipase C gamma / Q000378:metabolism; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt; D015398:Signal Transduction; D017923:Sodium-Hydrogen Exchangers / Q000235:genetics / Q000378:metabolism*; D013997:Time Factors; D000072258:Tumor Hypoxia; D059016:Tumor Microenvironment; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism*
chemical_list: D010750:Phosphoproteins; D017923:Sodium-Hydrogen Exchangers; C093376:sodium-hydrogen exchanger regulatory factor; C000588866:KDR protein, human; D040301:Vascular Endothelial Growth Factor Receptor-2; D051057:Proto-Oncogene Proteins c-akt; D051966:Phospholipase C gamma
keywords: NHERF1; PDZ protein; VEGFR; colorectal cancer; hypoxia