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Overview
Thioredoxin-1 (Trx-1), a low molecular weight redox protein, and its family members play critical roles in a cell's response to stress. Cancer cells exist in an environment of stress, including low levels of oxygen and nutrients, and become dependent on Trx-1. As a result of this dependency, many tumors have elevated levels of Trx-1, which contributes to increased cellular proliferation, resistance to cell death and increased angiogenesis.
Thioredoxin-1(Trx-1)
- Trx-1 regulates transcription factor activity and inhibits apoptosis inside the cell, promoting cell growth and survival
- Trx-1 interacts with growth factors (GF) outside the cell to stimulate cell growth
- Trx-1 overexpression is linked to aggressive tumor growth and poor prognosis
There are significant experimental and clinical data linking Trx to cancer and tumor growth. These data provide a cogent rationale for evaluating Trx-1 as a target for cancer drug development:
- Many tumors secrete Trx;
- Increased levels of Trx protein have been reported in a wide range of human cancers including hepatoma, lung, squamous cervical carcinoma, primary gastric cancers, and colorectal carcinomas;
- Trx stimulates the growth of a wide variety of human leukemia and solid tumor cell lines;
- Overexpression of Trx transforms normal cells into cancer cells;
- Trx is a potent inhibitor of apoptosis and provides a survival as well as a growth advantage to tumors;
- Elevated tumor Trx levels have been associated with decreased patient survival in colorectal cancer and NSCLC; and
- Elevated Trx levels cause a decrease in sensitivity of cells to cancer drugs such as doxorubicin (14 fold), vincristine (8 fold), cisplatin (5 fold), and cytosine arabinoside (13 fold). This suggests that overexpression of Trx in human tumors could be a cause of resistance to chemotherapy.
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