Nuclear envelope (NE) consists of outer nuclear membrane (ONM) and inner nuclear membrane (INM), which are separated by the perinuclear space and connected at the nuclear pore complex. Inner nuclear membrane proteins play a key role in cell cycle regulation, DNA repair and senescence, and cell migration in tumor formation and progression. However, the molecular mechanism of cancer invasiveness driven by inner nuclear membrane proteins remains to be determined by further study.
Recently, in a study titled “Inner nuclear membrane protein TMEM201 promotes breast cancer metastasis by positive regulating TGF β signaling” published in Oncogene, scientists found that a new type of inner nuclear membrane protein TMEM201 may promote breast cancer metastasis.
In addition to providing physical strength and stability to protect the nucleus, inner nuclear membrane proteins are also involved in the pathogenesis of cancer, the researchers said. According to this study, TMEM201, a type III inner nuclear membrane protein, is abundantly expressed in invasive breast cancer and is associated with a worse survival rate. The researchers discovered that as TMEM201 expression rose, it aided the process of epithelial-mesenchymal transformation (EMT) mediated by TGF, allowing breast cancer cells to migrate, invade, and survive. The findings reveal that there is a physical interaction between TMEM201 and SMAD2/3, which is required for SMAD2/3 phosphorylation.
These findings point to potential therapeutic strategies for invasive breast cancer that has a poor prognosis. The inner nuclear membrane protein TMEM201 may operate as a positive regulator of TGF β signal by interacting with SMAD2/3, broadening scientists’ understanding of the involvement of inner nuclear membrane protein in cancer cell biology and oncology as a whole.