Year: 2010
Type: article
Abstract: The aggressive course of pancreatic cancer is believed to reflect its unusually invasive and metastatic nature, which is associated with epidermal growth factor receptor (EGFR) overexpression and NF-kappaB activation. MicroRNAs (miRNA) have been implicated in the regulation of various pathobiological processes in cancer, including metastasis in pancreatic cancer and in other human malignancies. In this study, we report lower expression of miR-146a in pancreatic cancer cells compared with normal human pancreatic duct epithelial cells. Reexpression of miR-146a inhibited the invasive capacity of pancreatic cancer cells with concomitant downregulation of EGFR and the NF-kappaB regulatory kinase interleukin 1 receptor-associated kinase 1 (IRAK-1). Cellular mechanism studies revealed crosstalk between EGFR, IRAK-1, IkappaBalpha, NF-kappaB, and MTA-2, a transcription factor that regulates metastasis. Treatment of pancreatic cancer cells with the natural products 3,3'-diinodolylmethane (DIM) or isoflavone, which increased miR-146a expression, caused a downregulation of EGFR, MTA-2, IRAK-1, and NF-kappaB, resulting in an inhibition of pancreatic cancer cell invasion. Our findings reveal DIM and isoflavone as nontoxic activators of a miRNA that can block pancreatic cancer cell invasion and metastasis, offering starting points to design novel anticancer agents.
Source: Cancer Research
Language: English
Subfield: Cancer Research
Domain: Life Sciences
Open Access status: bronze
Awards: G1656582536, SPORE in Pancreatic Cancer, G3573105032, G437898191, RO1: A novel and targeted approach to inhibit invasion and angiogenesis, Targeting Akt/NF-kappa beta for Pancreatic Cancer Therapy, G7365431441, FoxM1: A molecular target in pancreatic cancer, G873604421, Molecular Mechanism of Genistein (Isoflavone) in Prostate Cancer
OpenAlex ID: W2142801414