Professor Ye Qinong JBC interprets cancer signals
Researchers from the Institute of Bioengineering of the Academy of Military Medical Sciences and the General Hospital of the People ’s Liberation Army confirmed that Memo (Mediator of ErbB2-driven cell motility) promotes extranuclear estrogen by interacting with growth factor receptors IGF1R and ErbB2 Estrogen receptor (ER) signal. The research findings were published in the July 16 issue of the Journal of Biochemistry (JBC). Qinong Ye, a researcher at the Institute of Bioengineering of the Academy of Military Medical Sciences, is the corresponding author of this paper. His main research direction is molecular biology of tumors.
Estrogen plays a vital role in the formation and progression of estrogen-related cancers such as breast cancer. Estrogen exerts its biological effects through the estrogen receptor α (ERα) and ERβ, and regulates the gene transcription network. ER belongs to the superfamily of ligand-activated transcription factors. It is generally believed that ER is a nuclear transcription factor that can be activated by ligands to bind to the estrogen-responsive element of the target gene. After binding to DNA, ER regulates target gene transcription by recruiting co-activators and co-repressors. Although most ERs mediate ligand-dependent and independent gene transcription in the nucleus, more and more research evidence clearly shows that a small percentage of ERs are located in the presence or absence of estrogen Or close to the plasma membrane, mediating rapid extranuclear function of ER cells. The extranuclear ER signaling pathway involves IGF1R and EGFR, leading to the activation of many signaling molecules such as MAPK, AKT, and intracellular second messengers. MAPK and AKT can phosphorylate Erα, thereby enhancing the transcriptional activity of Erα. In cultured cancer cells, Erα signaling initiated by the membrane mediates the proliferative effect of estrogen. However, until now the molecular mechanism by which extracellular ER exerts its functions is still not very clear.
Memo is a protein containing 197 amino acids and has no homology with any known signaling protein. Little is known about the biological function of Memo. Memo can interact with ErbB2, which is a necessary condition for breast cancer cell migration. ErbB2 is a member of the epidermal growth factor receptor tyrosine kinase family. Memo controlled the microtubule dynamics regulated by ErbB2.
In this article, the researchers reported confirming that Memo regulates the extranuclear function of ER. Memo interacted with ER physically and functionally. By interacting with growth factor receptors IGF1R and ErbB2, Memo mediates the extranuclear functions of ER, including the activation of MAPK and AKT, two important nuclear estrogen receptor growth-regulating protein kinases, which function in concert with nuclear ER. Memo regulates ER phosphorylation and estrogen response gene expression by activating MAPK and AKT. In addition, Memo promotes the growth of adherent-dependent and independent ER-positive breast cancer cells in vitro, which is a necessary condition for estrogen-induced breast tumor formation in nude mice.
These findings confirm that Memo is a new component of extracellular ER signaling bodies, indicating that Memo plays an important role in regulating the growth of ER-positive breast cancer cells.
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