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Oncogenesis. 2018 Jul 6;7(7):52. doi: 10.1038/s41389-018-0061-7.

FOXC1 plays a crucial role in the growth of pancreatic cancer.

Author information

1
Center of Emphasis in Cancer Research, Department of Biomedical Sciences, Paul L. Foster School of Medicine, Texas Tech University Health Sciences Center El Paso, El Paso, Texas, 79905, USA.
2
Graduate School of Biomedical Sciences, Texas Tech University Health Sciences Center El Paso, El Paso, Texas, 79905, USA.
3
The University of Texas at El Paso, El Paso, TX, 79968, USA.
4
Center of Emphasis in Cancer Research, Department of Biomedical Sciences, Paul L. Foster School of Medicine, Texas Tech University Health Sciences Center El Paso, El Paso, Texas, 79905, USA. rajkumar.lakshmanaswamy@ttuhsc.edu.
5
Graduate School of Biomedical Sciences, Texas Tech University Health Sciences Center El Paso, El Paso, Texas, 79905, USA. rajkumar.lakshmanaswamy@ttuhsc.edu.

Abstract

IGF-1R signaling controls various vital cellular functions and this signaling is deregulated in many cancers, including pancreatic cancer. Several efforts have mainly focused on inhibiting the IGF-1R signaling cascade. The outcomes of these focused preclinical studies have been positive, whereas clinical trials of IGF-1R inhibitors in pancreatic cancer have failed, raising the questions about this therapeutic approach. This necessitates a better understanding of the role of IGF-1R signaling in pancreatic cancer. We investigated the impact of IGF-1R signaling on crucial transcription factors and identified the FOXC1 as one of the crucial regulator of IGF-1R signaling. We employed genetic approaches to overexpress and silence FOXC1 in pancreatic cancer cells. Our results demonstrate that IGF-1R and FOXC1 seem to positively regulate each other. Further, FOXC1 increased the metastatic abilities of pancreatic cancer cells by enhancing cell proliferation, migration, invasion, epithelial-to-mesenchymal transition, and angiogenesis. The data from xenograft experiments further established the importance of FOXC1 in pancreatic tumorigenesis. In conclusion, FOXC1 is a potent oncogenic transcription factor, which promotes pancreatic cancer growth and metastasis. Thus, targeting FOXC1 could be a potential therapeutic strategy against pancreatic cancer.

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