title: Targeting insulin-like growth factor 1 receptor inhibits pancreatic cancer growth and metastasis.
abstract: Pancreatic cancer is one of the most lethal cancers. Increasing incidence and mortality indicates that there is still much lacking in detection and management of the disease. This is partly due to a lack of specific symptoms during early stages of the disease. Several growth factor receptors have been associated with pancreatic cancer. Here, we have investigated if an RNA interference approach targeted to IGF-IR could be effective and efficient against pancreatic cancer growth and metastasis. For that, we evaluated the effects of IGF-1R inhibition using small interfering RNA (siRNAs) on tumor growth and metastasis in HPAC and PANC-1 pancreatic cancer cell lines. We found that silencing IGF-1R inhibits pancreatic cancer growth and metastasis by blocking key signaling pathways such AKT/PI3K, MAPK, JAK/STAT and EMT. Silencing IGF-1R resulted in an anti-proliferative effect in PANC-1 and HPAC pancreatic cancer cell lines. Matrigel invasion, transwell migration and wound healing assays also revealed a role for IGF-1R in metastatic properties of pancreatic cancer. These results were further confirmed using Western blotting analysis of key intermediates involved in proliferation, epithelial mesenchymal transition, migration, and invasion. In addition, soft agar assays showed that silencing IGF-1R also blocks the colony forming capabilities of pancreatic cancer cells in vitro. Western blots, as well as, flow cytometric analysis revealed the induction of apoptosis in IGF-1R silenced cells. Interestingly, silencing IGF-1R also suppressed the expression of insulin receptor β. All these effects together significantly control pancreatic cancer cell growth and metastasis. To conclude, our results demonstrate the significance of IGF-1R in pancreatic cancer.
authors.affiliation: Center of Excellence in Cancer Research, Department of Biomedical Sciences MSB1, Texas Tech University Health Sciences Center, Paul L. Foster School of Medicine, El Paso, Texas, United States of America.
authors.forename: Ramadevi
authors.initials: R
authors.lastname: Subramani
authors.affiliation: Center of Excellence in Cancer Research, Department of Biomedical Sciences MSB1, Texas Tech University Health Sciences Center, Paul L. Foster School of Medicine, El Paso, Texas, United States of America.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Lopez-Valdez
authors.affiliation: Center of Excellence in Cancer Research, Department of Biomedical Sciences MSB1, Texas Tech University Health Sciences Center, Paul L. Foster School of Medicine, El Paso, Texas, United States of America.
authors.forename: Arunkumar
authors.initials: A
authors.lastname: Arumugam
authors.affiliation: Center of Excellence in Cancer Research, Department of Biomedical Sciences MSB1, Texas Tech University Health Sciences Center, Paul L. Foster School of Medicine, El Paso, Texas, United States of America.
authors.forename: Sushmita
authors.initials: S
authors.lastname: Nandy
authors.affiliation: Center of Excellence in Cancer Research, Department of Biomedical Sciences MSB1, Texas Tech University Health Sciences Center, Paul L. Foster School of Medicine, El Paso, Texas, United States of America.
authors.forename: Thiyagarajan
authors.initials: T
authors.lastname: Boopalan
authors.affiliation: Center of Excellence in Cancer Research, Department of Biomedical Sciences MSB1, Texas Tech University Health Sciences Center, Paul L. Foster School of Medicine, El Paso, Texas, United States of America.
authors.forename: Rajkumar
authors.initials: R
authors.lastname: Lakshmanaswamy
mesh_terms: D017209:Apoptosis / Q000235:genetics; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics; D055785:Gene Knockdown Techniques; D006801:Humans; D020935:MAP Kinase Signaling System / Q000235:genetics; D058990:Molecular Targeted Therapy; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000473:pathology*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D017526:Receptor, IGF Type 1 / Q000172:deficiency* / Q000235:genetics*
chemical_list: D034741:RNA, Small Interfering; D017526:Receptor, IGF Type 1