title: BMP signaling pathways affect differently migration and invasion of esophageal squamous cancer cells.
abstract: Bone morphogenetic proteins (BMPs) are broadly involved in normal embryo development and abnormal pathological process such as cancer. The complexity and diversity of BMPs and their signaling pathways impose quite different or even conflicting effects on clinical traits of tumors. The aim of the present study was to investigate whether different BMPs, including BMP2, BMP4, BMP6 and BMP7, influence esophageal squamous cancer cell (ESCC) growth, invasion and metastasis. BMP6 and type I receptor ALK2 and type II receptor BMPRII, ActRIIA and ActRIIB were expressed in all ESCC cell lines. In addition, adenovirus-mediated BMP overexpression did not affect ECA-109 cell growth. BMP6/7 overexpression increased ECA-109 cell invasion and metastasis, activated SMAD1/5/8 signal pathway and induced downstream gene ID1 expression. While BMP2/4 overexpression reduced ECA-109 cell invasion and metastasis and obviously promoted ERK1/2, P-38 and JNK activation with weak SMAD1/5/8 phosphorylation. When BMP6/7 favorite type I receptor ALK2 or type II receptor BMPRII was interfered with by dominant-negative mutation, BMP6/7-induced invasion and metastasis augmentation disappeared. Further investigation on clinical ESCC samples and non-tumorous adjacent tissue found that tumors with triple-positive BMP6, ALK2 and BMPRII had deeper growth than tumors with only BMP6 expression. These results suggested that different BMPs distinctly affected esophageal squamous cancer cell invasion and metastasis by employing different signal pathways.
authors.affiliation: Clinical Biochemistry Laboratory, Medical Diagnostic Department of Henan Provincial People's Hospital, Zhengzhou, Henan 450000, P.R. China.
authors.forename: Min
authors.initials: M
authors.lastname: Hu
authors.affiliation: Clinical Biochemistry Laboratory, Medical Diagnostic Department of Henan Provincial People's Hospital, Zhengzhou, Henan 450000, P.R. China.
authors.forename: Facai
authors.initials: F
authors.lastname: Cui
authors.affiliation: Clinical Biochemistry Laboratory, Medical Diagnostic Department of Henan Provincial People's Hospital, Zhengzhou, Henan 450000, P.R. China.
authors.forename: Fengzhen
authors.initials: F
authors.lastname: Liu
authors.affiliation: Clinical Biochemistry Laboratory, Medical Diagnostic Department of Henan Provincial People's Hospital, Zhengzhou, Henan 450000, P.R. China.
authors.forename: Jinlin
authors.initials: J
authors.lastname: Wang
authors.affiliation: Clinical Biochemistry Laboratory, Medical Diagnostic Department of Henan Provincial People's Hospital, Zhengzhou, Henan 450000, P.R. China.
authors.forename: Xiaoxia
authors.initials: X
authors.lastname: Wei
authors.affiliation: Clinical Biochemistry Laboratory, Medical Diagnostic Department of Henan Provincial People's Hospital, Zhengzhou, Henan 450000, P.R. China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Li
mesh_terms: D030201:Activin Receptors, Type I / Q000096:biosynthesis* / Q000235:genetics; D000256:Adenoviridae / Q000235:genetics; D055396:Bone Morphogenetic Protein 2 / Q000096:biosynthesis / Q000235:genetics; D055415:Bone Morphogenetic Protein 4 / Q000096:biosynthesis / Q000235:genetics; D055418:Bone Morphogenetic Protein 6 / Q000096:biosynthesis / Q000235:genetics*; D055419:Bone Morphogenetic Protein 7 / Q000096:biosynthesis / Q000235:genetics; D052006:Bone Morphogenetic Protein Receptors, Type II / Q000096:biosynthesis* / Q000235:genetics; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D004938:Esophageal Neoplasms / Q000235:genetics* / Q000473:pathology; D000077277:Esophageal Squamous Cell Carcinoma; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D009361:Neoplasm Invasiveness / Q000235:genetics / Q000473:pathology; D009362:Neoplasm Metastasis; D015398:Signal Transduction / Q000235:genetics; D051898:Smad1 Protein / Q000096:biosynthesis / Q000235:genetics
chemical_list: C525718:BMP2 protein, human; C525809:BMP4 protein, human; C525816:BMP6 protein, human; C525819:BMP7 protein, human; D055396:Bone Morphogenetic Protein 2; D055415:Bone Morphogenetic Protein 4; D055418:Bone Morphogenetic Protein 6; D055419:Bone Morphogenetic Protein 7; C497399:SMAD1 protein, human; D051898:Smad1 Protein; C425423:ACVR1 protein, human; D030201:Activin Receptors, Type I; C498218:BMPR2 protein, human; D052006:Bone Morphogenetic Protein Receptors, Type II