The Pathway Of Lung Cancer Progression

Targeting a protein that enhances the invasiveness of cancer cells could help treat lung cancer, researchers say.

AsianScientist (Oct. 24, 2017) – In a study published in Nature Communications, researchers from Nanjing University in China have identified an enzyme that promotes lung cancer progression. These findings indicate that epigenetic modulation plays a crucial role in lung cancer, implying a new therapeutic target for treatment.

Histone modification is known to be involved in cell growth. In this study, researchers investigated the role of NatD, an enzyme that mediates the N-alpha-terminal acetylation (Nt-acetylation) of histone H4, in lung cancer. They found that NatD is commonly upregulated in primary human lung cancer tissues where its expression level correlates with enhanced invasiveness and poor clinical outcomes.

Further investigation showed that NatD promotes the invasion of healthy tissue by regulating the epithelial-mesenchymal transition (EMT) of cancer cells through epigenetic control of a transcription factor called Slug. Nt-acetylation of histone H4 was found to interfere with the phosphorylation of the histone. Conversely, blocking Nt-acetylation encouraged the binding of other proteins to histone H4, resulting in increased phosphorylation of the histone and epigenetic reprogramming.

“These studies have demonstrated that NatD promotes the migratory and invasive capabilities of lung cancer cells both in vitro and in vivo. Thus, depletion of NatD suppresses the EMT of lung cancer cells via repression of the expression of transcription factor Slug” said Dr. Quan Zhao, professor of Biochemistry at the School of Life Sciences, Nanjing University.

“Revealing this new epigenetic pathway (NatD/Slug/EMT) is important to better understand the individual steps of metastasis formation and may help predict at an early stage whether the tumor will spread.”

In the future Zhao and his colleagues want to further investigate the role of NatD more closely in the process of invasion-metastasis of lung cancer and other tumors. They will also screen for biochemical blockers of NatD which may also have applications in lung cancer and other invasive tumor treatments.

The article can be found at: Ju et al. (2017) NatD Promotes Lung Cancer Progression by Preventing Histone H4 Serine Phosphorylation to Activate Slug Expression.


Source: Nanjing University; Photo: Shutterstock.
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