BMP2 induces PANC-1 cell invasion by MMP-2 overexpression through ROS and ERK.
The emerging roles of bone morphogenetic proteins (BMPs) in the initiation and progression of multiple cancers have drawn great attention in cancer research. We hypothesized that BMP2 promotes cancer metastasis by modulating MMP-2 secretion and activity through intracellular ROS regulation and ERK activation in human pancreatic cancer. Our data show that stimulation of PANC-1 cells with BMP2 induced MMP-2 secretion and activation, associated with decreased E-cadherin expression, resulting in epithelial-to-mesenchymal transformation (EMT) and cell invasion. Blockade of ROS by the ROS scavenger, 2-MPG, abolished cell invasion, inhibited the EMT process and decreased MMP-2 expression, suggesting ROS accumulation caused an increase in MMP-2 expression in BMP2-stimulated PANC-1 cell invasion. Furthermore, treatment of PANC-1 cells with 2-MPG or ERK inhibitor PD98059 reduced the phosphorylation of ERK, resulting in attenuation of BMP2-induced cell invasion and MMP-2 activation. Taken together, these results suggest that BMP2 induces the cell invasion of PANC-1 cells by enhancing MMP-2 secretion and acting through ROS accumulation and ERK activation.
Department of Gastroenterology, Ruijin Hospital, Shanghai Jiaotong University, Shanghai, China.
Jun
J
Liu
Qi-Wen
QW
Ben
Wei-Yan
WY
Yao
Jian-Jun
JJ
Zhang
Da-Fan
DF
Chen
Xiang-Yi
XY
He
Lei
L
Li
Yao-Zong
YZ
Yuan
D055396:Bone Morphogenetic Protein 2 / Q000378:metabolism* / Q000494:pharmacology; D045744:Cell Line, Tumor; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects / Q000502:physiology; D006801:Humans; D020935:MAP Kinase Signaling System; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D009361:Neoplasm Invasiveness / Q000473:pathology / Q000503:physiopathology; D010190:Pancreatic Neoplasms / Q000378:metabolism* / Q000473:pathology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D015398:Signal Transduction
C525718:BMP2 protein, human; D055396:Bone Morphogenetic Protein 2; D017382:Reactive Oxygen Species; D011994:Recombinant Proteins; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2