Abstract
Colon cancer has a five-year survival of 64.7%, and about 50,000 people are expected to die from colon cancer this year. Patients with metastatic colorectal cancer have a significantly worse prognosis, a 12.9% five -year survival. This emphasizes the need for strategies to inhibit the growth and metastases of colorectal cancer. Prostate apoptosis response protein 4 (Par-4) is a pro-apoptotic protein that has been shown to mediate apoptosis in response to stimuli, such as chemotherapeutics and radiation. Recombinant Par-4 protein has been shown to reduce the occurrence of Lewis lung carcinoma metastases in-vivo; however, the mechanism by which Par-4 can inhibit metastasis has not been elucidated. In this study, human colon cancer cell lines SW480 and SW620 were transfected with Par-4 plasmid or anti-Par-4 shRNA, and the effect on metastasis was examined. Par-4 overexpression inhibited cell migration and invasion, while Par-4 knockdown promoted it. Moreover, the morphology of SW620 cells was altered when Par-4 levels were increased. The change was characteristic of a mesenchymal-to-epithelial transition (MET) in these cells. MET can be induced by upregulation of E-cadherin expression, and RT-PCR and Western blot analyses showed that E-cadherin mRNA and protein levels, respectively, were increased in the Par-4 overexpressing cells concomitant with a decrease in vimentin. The results of this study demonstrate the potential of Par-4 in colon cancer therapy, not only in primary tumors but also in metastatic cells. DOI : 10.14302/issn.2471-7061.jcrc-14-574 Corresponding Author: Rosalyn B. Irby, Ph.D. 500 University Drive Hershey, PA 17033 Tel: 717-531-5035 Email: rirby@hmc.psu.edu
Highlights
Colon cancer has a five-year survival of 64.7%, and about 50,000 people are expected to die from colon cancer this year
Despite increases in but it may inhibit their metastasis. This was length of survival with the combination of targeted suggested in a previous study, where mRNA and agents, including anti-epidermal growth factor receptor microRNA microarray analyses on Par-4 overexpressing and anti-vascular endothelial growth factor agents, with HT-29 colorectal cancer cells showed that Par-4 altered a 5-fluorouracil based regimen, patients with metastases the expression of genes involved in cell movement, are expected to survive for 2 years
RNA was isolated from mock and Par-4transfected SW620 cells using RNeasy kit (Qiagen). cDNA was synthesized using a High Capacity cRNA reverse transcription kit (Applied colorectal cancer cell line by stably transfecting cells with a plasmid vector encoding human Par-4 (Fig 1a and b)
Summary
Colon cancer has a five-year survival of 64.7%, and about 50,000 people are expected to die from colon cancer this year. Despite increases in but it may inhibit their metastasis This was length of survival with the combination of targeted suggested in a previous study, where mRNA and agents, including anti-epidermal growth factor receptor microRNA microarray analyses on Par-4 overexpressing and anti-vascular endothelial growth factor agents, with HT-29 colorectal cancer cells showed that Par-4 altered a 5-fluorouracil based regimen, patients with metastases the expression of genes involved in cell movement, are expected to survive for 2 years. This underscores including cell migration and invasion[16]. Par-4 overexpression increases apoptosis in response to the chemotherapeutic agent 5-fluorouracil[9]
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