Nerve growth factor modulates the tumor cells migration in ovarian cancer through the WNT/β-catenin pathway.
Nerve growth factor (NGF)/nerve growth factor receptors (NGFRs) axis and canonical WNT/β-catenin pathway have shown to play crucial roles in tumor initiation, progression and prognosis. But little did we know the relationship between them in modulation of tumor progress. In this report, we found that NGF/NGFRs and β-catenin were coexpression in ovarian cancer cell lines, and NGF can decrease the expression level of β-catenin and affect its activities, which may be related to the NGF-induced down-regulation of B-cell CLL/lymphoma 9-like (BCL9L, BCL9-2). Furthermore, NGF can also increase or decrease the downstream target gene expression levels of WNT/β-catenin depending on the cell types. Especially, we created a novel in vitro cell growth model based on a microfluidic device to intuitively observe the effects of NGF/NGFRs on the motility behaviors of ovarian cancer cells. The results showed that the migration area and maximum distance into three dimensional (3D) matrigel were decreased in CAOV3 and OVCAR3 cells, but increased in SKOV3 cells following the stimulation with NGF. In addition, we found that the cell colony area was down-regulated in CAOV3 cells, however, it was augmented in OVCAR3 cells after treatment with NGF. The inhibitors of NGF/NGFRs, such as Ro 08-2750, K252a and LM11A-31,can all block NGF-stimulated changes of gene expression or migratory behavior on ovarian cancer cells. The different results among ovarian cancer cells illustrated the heterogeneity and complexity of ovarian cancer. Collectively, our results suggested for the first time that NGF is functionally linked to β-catenin in the migration of human ovarian cancer cells, which may be a novel therapeutic perspective to prevent the spread of ovarian carcinomas by studying the interaction between NGF/NGFRs and canonical WNT/β-catenin signaling.
Key laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing, China.|School of Education, Chongqing Normal University, Chongqing, China.
Bo
B
Li
Key laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing, China.
Shaoxi
S
Cai
Key laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing, China.
Yi
Y
Zhao
College of Life Sciences, Chongqing Normal University, Chongqing, China.
Qiyi
Q
He
College of Life Sciences, Chongqing Normal University, Chongqing, China.
Xiaodong
X
Yu
Key laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing, China.
Longcong
L
Cheng
College of Life Sciences, Chongqing Normal University, Chongqing, China.
Yingfeng
Y
Zhang
College of Chemistry, Chongqing Normal University, Chongqing, China.
Xiancheng
X
Hu
Key laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing, China.
Ming
M
Ke
Key laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing, China.
Sijia
S
Chen
Key laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing, China.
Misha
M
Zou
D000970:Antineoplastic Agents / Q000494:pharmacology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D004268:DNA-Binding Proteins / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D056656:Lab-On-A-Chip Devices; D046210:Microfluidic Analytical Techniques / Q000295:instrumentation; D009361:Neoplasm Invasiveness; D020932:Nerve Growth Factor / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D010766:Phosphorylation; D017475:Receptors, Nerve Growth Factor / Q000819:agonists / Q000235:genetics / Q000378:metabolism; D013997:Time Factors; D014157:Transcription Factors / Q000378:metabolism; D060449:Wnt Signaling Pathway / Q000187:drug effects*; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism*
D000970:Antineoplastic Agents; C495498:BCL9L protein, human; C495270:CTNNB1 protein, human; D004268:DNA-Binding Proteins; C502240:NGF protein, human; D017475:Receptors, Nerve Growth Factor; D014157:Transcription Factors; D051176:beta Catenin; D020932:Nerve Growth Factor
3D microfluidic device; NGF; NGFRs; WNT/β-catenin pathway; migration