Researchers from the National Cancer Institute (NCI) published an article titled "The Pivotal Role of IKKα in the Development of Spontaneous Lung Squamous Cell Carcinomas" and designed a genetically engineered mouse that can be used to study humans The study of lung squamous cell carcinoma helps to screen drugs against this cancer. The research results were published in the journal Cancer Cell. Leading the study is the Chinese female professor Yinling Hu (Ninling Hu) of the National Cancer Institute. The research team is currently identifying the downstream role of IKKa for keratinocyte differentiation and proliferation switches, and is still investigating whether it is caused by mutations. Whether IKKa leads to uncontrolled growth of keratinocytes can help clarify the mechanism of cancer development in a specific environment.
Squamous cell carcinoma (SCC) is a malignant epithelial tumor derived from bronchial epithelium that can exhibit keratinization and / or intercellular bridge features. This is a type of non-small cell lung cancer, which is the most common form of lung cancer, with a five-year survival rate of about 15%. In this article, the researchers constructed a new mouse model to find molecular targets, such as IKK-alpha (IKK-α), IKK-α kinase is the key to the development of mouse embryo skin. Mice lacking IKK exhibited significant epidermal hyperplasia, cells lacked final differentiation, and mice died due to this severe skin loss.
Professor Hu's research group found that IK-Kα can prevent a cell cycle critical "checkpoint" gene from being silenced. The article points out that when DNA in the cell is damaged, the tumor suppressor gene p53 will activate the checkpoint gene 14-3-3 -Sigma expression. The protein expressed by the checkpoint gene can effectively prevent the division of the damaged cell, so that the genetic error in the copy process can be corrected in time, so that the error is not transmitted to the progeny cells. On this basis, the researchers began to look for similarities in SCC cells and similarities in the cancer microenvironment between human lung SCCs and mouse lung SCCs. As a result, they found that the reduction of IKK-α can promote the increase of oncogenic protein expression and reduce the expression of tumor suppressor protein in lung SCCs.
And the researchers also pointed out that mice with reduced IKK-α will have an increase in lung inflammatory cells, which is also a major reason for the development of lung SCC. Professor Hu's research group has been conducting research on IKK-α for the past ten years, and they have also discovered the role of IKK-α in the cell cycle. Missing mouse model. It was found that this protein monitors the proliferation of keratinocytes and induces terminal differentiation. And even if the epidermis contains only a very low level of IKKα, it is enough for the embryonic skin to develop normally.
The researchers believe that IKKα is a switch between proliferation and differentiation, which is necessary to maintain the dynamic rest or stability of the skin and prevent skin cancer. Research shows the importance of IKKα for maintaining skin homeostasis and preventing skin cancer, and also reveals the mechanism of IKKα in these processes.
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