Abstract:
:Deregulation of insulin-like growth factor-1 receptor (IGF-1R) and focal adhesion kinase (FAK) signaling pathways plays an important role in cancer cell proliferation and metastasis. In pancreatic cancer cells, the crosstalk and compensatory mechanisms between these two pathways reduce the efficacy of the treatments that target only one of the pathways. Ablation of IGF-1R signaling by siRNA showed minimal effects on the survival and growth of pancreatic cancer cells. An increased activity of FAK pathway was seen in these cells after IGF-1R knockdown. Further inhibition of FAK pathway using Y15 significantly decreased cell survival, adhesion, and promoted apoptosis. The combination of Y15 treatment and IGF-1R knockdown also showed significant antitumor effect in vivo. The current study demonstrates the importance of dual inhibition of both these signaling pathways as a novel strategy to decrease both in vitro and in vivo growth of human pancreatic cancer.
journal_name
Mol Carcinogjournal_title
Molecular carcinogenesisauthors
Zheng D,Golubovskaya V,Kurenova E,Wood C,Massoll NA,Ostrov D,Cance WG,Hochwald SNdoi
10.1002/mc.20590subject
Has Abstractpub_date
2010-02-01 00:00:00pages
200-9issue
2eissn
0899-1987issn
1098-2744journal_volume
49pub_type
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