Phosphatidylinositol diphosphate (PIP2) is a phospholipid that is essential for epithelial cell-cell adhesion and maintenance of cell identity. Somatic cells in multicellular organisms adhere to each other to form tissues and play various physiological functions Epithelial cells are types of cells that line the surface of your body. They are found in your skin, blood vessels, urinary tract and organs. Epithelial cells form our skin and lining surfaces, such as the intestines and other ducts, and protect internal organs.
In order to maintain the integrity and normal function of an organism, it is important that these cells remain interconnected. They do this through specific types of cell connections. These connections are characterized by proteins, which also help maintain the characteristics of cells.
The loss of these proteins from the cell surface causes them to lose their identity as epithelial cells, prompting them to transform into interstitial cells (through a process called epithelial mesenchymal transformation, or EMT), and then they develop into cancer and fibrosis.
These cancer cells only loosely adhere to each other (given that the proteins that help maintain cell adhesion are now lost), so they may separate from each other, migrate into the blood, and lead to cancer metastasis (spread to other parts of the body).
Now, although the role of proteins in maintaining cell properties has been well studied, we can't help asking -- does lipids (fat molecules) also play a role in characterizing cells and preventing EMT?
Under the guidance of Dr. Nakamura and Dr. Kaori Kanemaru, scientists from Tokyo University of Science (TUS), Tokyo Pharmaceutical University and School of life sciences, Tokyo Medical University and Dental University, Akita University, Hokkaido University and Kobe University tried to find the answer to this question.
Phospholipid PIP2 plays a key role in maintaining the characteristics of epithelial cells
"We know that lipids are an important class of biomolecules that are necessary for some cell functions. One of these lipids, phosphatidylinositol, forms a phospholipid called phosphatidylinositol diphosphate (PIP2)," Dr. Nakamura, an associate professor from Tokyo University of science, delved into the topic. He told us that PIP2 is important because it is crucial for the formation of signaling molecules that regulate cell proliferation, survival and migration. We have evidence that more PIP2 is found in the epidermal layer of the skin, so it can be assumed that this phospholipid contributes to the characteristics and characteristics of epithelial cells. "
Their findings will be published in the journal Nature communications today (May 9, 2022). The paper describes how the team used a series of analytical techniques, including chromatography, mass spectrometry, immunofluorescence, retroviral expression and real-time quantitative PCR, to confirm that PIP2 plays a key role in determining the characteristics of epithelial cells.
"We see that when PIP2 is depleted from the cell membrane, epithelial cells lose their properties. On the other hand, when PIP2 is produced in its plasma membrane, osteosarcoma cells (belonging to cancer, non epithelial cells) acquire epithelial like properties," Dr. Nakamura said with an excited expression. The team was also able to show that PIP2 regulates these epithelial characteristics by recruiting Par3, a protein that guides intracellular vesicles, to the plasma membrane. Once it enters the plasma membrane, Par3 promotes the formation of adhesion junctions (one of the cell junctions discussed above) and fixes adjacent cells together. This partially prevents EMT, thereby preventing the development of cancer.
"Therefore, in theory, the partial inhibition of EMT by PIP2 can prevent the development of cancer, making this phospholipid an attractive target molecule for anticancer therapy."
The research of tus opens up a new way for the development of anticancer drugs.