Poor oxygen levels inside tumours promotes their progression through direct activation of TWIST, a key protein involved in both embryonic development and metastasis. A study published online in Nature Cell Biology identifies a pathway that could be active in several types of cancer, and the importance of using certain protein inhibitors for tumour treatment.
Tumour growth is often accompanied by low levels of oxygen or hypoxia, which has been closely associated with resistance to treatment and the spread of disease from one area to another, known as metastasis. Hypoxic cells produce high levels of a protein known as HIF-1alpha, which controls the levels of several genes that are important in the cellular response to low oxygen. Kou-Juey Wu and colleagues have found that TWIST is regulated directly by this protein and that it mediates hypoxia-induced tumour progression and metastasis.
The team discovered that Increased cellular production of TWIST by HIF-1alpha was associated with enhanced migration and invasion of cancer cells. Intravenous injection of HIF-1alpha-producing cells into mice induced cell migration and the formation of tumours in the lungs; with both effects requiring TWIST. Analysis of samples from patients with primary head and neck squamous cell carcinomas revealed that the presence of HIF-1alpha and TWIST is associated with a faster onset of metastasis and poorer prognosis.
Kou-Juey Wu (National Yang-Ming University, Taipei, Taiwan)
Abstract available online.
(C) Nature Cell Biology press release.
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