title: A novel strategy to inhibit FAK and IGF-1R decreases growth of pancreatic cancer xenografts.
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.
authors.affiliation: Department of Surgery, University of Florida, Gainesville, Florida, USA.
authors.forename: Donghang
authors.initials: D
authors.lastname: Zheng
authors.forename: Vita
authors.initials: V
authors.lastname: Golubovskaya
authors.forename: Elena
authors.initials: E
authors.lastname: Kurenova
authors.forename: Cheng
authors.initials: C
authors.lastname: Wood
authors.forename: Nicole A
authors.initials: NA
authors.lastname: Massoll
authors.forename: David
authors.initials: D
authors.lastname: Ostrov
authors.forename: William G
authors.initials: WG
authors.lastname: Cance
authors.forename: Steven N
authors.initials: SN
authors.lastname: Hochwald
mesh_terms: D000818:Animals; D001483:Base Sequence; D017931:DNA Primers; D005260:Female; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D008819:Mice, Nude; D010190:Pancreatic Neoplasms / Q000201:enzymology / Q000378:metabolism / Q000473:pathology*; D034741:RNA, Small Interfering; D017451:Receptors, Somatomedin / Q000037:antagonists & inhibitors*; D014183:Transplantation, Heterologous
chemical_list: D017931:DNA Primers; D034741:RNA, Small Interfering; D017451:Receptors, Somatomedin; D051416:Focal Adhesion Protein-Tyrosine Kinases