Urokinase-targeted recombinant bacterial protein toxins – a rationally designed and engineered anticancer agent for cancer therapy

doi:10.1007/s11515-008-0074-2

Front Biol Chin

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Research Article

Urokinase-targeted recombinant bacterial protein toxins – a rationally designed and engineered anticancer agent for cancer therapy

Yizhen LIU¹, Shi-Yan LI²(

)

1. Department of Biomedical Sciences, Colorado State University, Font Collins; 2. Cancer Research Institute of Scott & White, Temple

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Abstract

Urokinase-targeted recombinant bacterial protein toxins are a sort of rationally designed and engineered anticancer recombinant fusion proteins representing a novel class of agents for cancer therapy. Bacterial protein toxins have long been known as the primary virulence factor(s) for a variety of pathogenic bacteria and are the most powerful human poisons. On the other hand, it has been well documented that urokinase-type plasminogen activator (uPA) and urokinase plasminogen activator receptor (uPAR), making up the uPA system, are overexpressed in a variety of human tumors and tumor cell lines. The expression of uPA system is highly correlated with tumor invasion and metastasis. To exploit these characteristics in the design of tumor cell-selective cytotoxins, two prominent bacterial protein toxins, i.e., the diphtheria toxin and anthrax toxin are deliberately engineered through placing a sequence targeted specifically by the uPA system to form anticancer recombinant fusion proteins. These uPA system-targeted bacterial protein toxins are activated selectively on the surface of uPA system-expressing tumor cells, thereby killing these cells. This article provides a review on the latest progress in the exploitation of these recombinant fusion proteins as potent tumoricidal agents. It is perceptible that the strategies for cancer therapy are being innovated by this novel therapeutic approach.

Keywords urokinase-type plasminogen activator (uPA) diphtheria toxin, anthrax toxin recombinant fusion proteins cancer therapy

Corresponding Author(s): LI Shi-Yan,Email:sli@swmail.sw.org

Issue Date: 05 March 2009

Cite this article:

Yizhen LIU,Shi-Yan LI. Urokinase-targeted recombinant bacterial protein toxins – a rationally designed and engineered anticancer agent for cancer therapy[J]. Front Biol Chin, 0, (): 1-6.

URL:

https://academic.hep.com.cn/fib/EN/10.1007/s11515-008-0074-2
https://academic.hep.com.cn/fib/EN/Y0/V/I/1

Fig0 Uptake and activity of the diphtheria toxin in eukaryotic cells. The figure is revised from Todar's Online Textbook of Bacteriology. A represents the A/B toxin's A (catalytic) domain; B is the B (receptor) domain; T is the hydrophobic domain that inserts into the cell membrane.

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