MSGID: 1:317/3 6279eaac   
   PID: hpt/lnx 1.9.0-cur 2019-01-08   
   TID: hpt/lnx 1.9.0-cur 2019-01-08   
    Getting sticky with it: Phospholipid found to play a key role in   
   epithelial cell adhesion    
    Phosphatidylinositol bisphosphate (PIP2) is essential for epithelial   
   cell-cell adhesion and maintaining cellular identity    
      
     Date:   
         May 9, 2022   
     Source:   
         Tokyo University of Science   
     Summary:   
         Cells have certain proteins that help them adhere to each   
         other while covering body surfaces and organs. Loss of these   
         identifying proteins could result in cellular progression towards   
         cancer and, subsequently, metastasis. However, lipids may play   
         a role in maintaining cellular identity as well. Scientists have   
         now identified the role of PIP2, a phospholipid, in maintaining   
         epithelial cell-cell adhesion and cellular identity. Their findings   
         will help develop strategies aimed at suppressing metastasis.   
      
      
      
   FULL STORY   
   ==========================================================================   
   In multicellular organisms, body cells adhere to each other to form   
   tissues that perform various physiological functions. Epithelial cells   
   form our skin and lining surfaces, such as the gut and other ducts, and   
   protect our internal organs. To maintain the integrity of an organism   
   and function properly, it is important for these cells to remain   
   attached to each other. They do so through specific types of cellular   
   junctions. These junctions are characterized by proteins, which also   
   help in maintaining cellular identity. The loss of these proteins from   
   cell surfaces causes them to lose their identity as epithelial cells,   
   prompting their transformation into mesenchymal cells (through a process   
   known as epithelial-mesenchymal transformation, or EMT), and subsequently,   
   their progression towards cancer and fibrosis. These cancerous cells are   
   only loosely adherent to each other (given that the proteins that helped   
   maintain cellular adhesion are now lost), so they may separate from each   
   other, migrate into the bloodstream, and cause the cancer to metastasize   
   (spread to other parts of the body).   
      
      
   ==========================================================================   
   Now, while the role of proteins in maintaining cellular identity is   
   well- researched, we can't help but wonder-do lipids (fatty molecules)   
   also play a role in characterizing cells and preventing EMT?  Under the   
   guidance of Dr. Yoshikazu Nakamura and Dr. Kaori Kanemaru, researchers   
   from Tokyo University of Science (TUS), Tokyo University of Pharmacy and   
   Life Sciences, Tokyo Medical and Dental University, Akita University,   
   Hokkaido University, and Kobe University have tried to find an answer   
   to this question.   
      
   "We know lipids are an important class of biomolecules, necessary for   
   certain cellular functions. One such lipid, a phosphatidylinositol, forms   
   a phospholipid called phosphatidylinositol bisphosphate (PIP2)," Associate   
   Professor Dr. Nakamura from TUS dives into the topic. He tells us that   
   PIP2 is important because it is crucial for the formation of signaling   
   molecules that regulate cell proliferation, survival, and migration. "We   
   had evidence that higher amounts of PIP2 were found in the epidermal   
   layer of skin, so we hypothesized that this phospholipid contributed to   
   the properties and characterization of epithelial cells."  The findings   
   from their study have been published in Nature Communications. The   
   paper describes how the team used a battery of analytical techniques   
   including chromatography, mass spectroscopy, immunofluorescence,   
   retroviral expression, and real-time quantitative PCR to confirm that   
   PIP2 plays a critical role in the determination of epithelial identity.   
      
   "We saw that epithelial cells lost their properties when PIP2 was   
   depleted from their cell membranes. On the other hand, osteosarcoma cells   
   (which are cancerous, non-epithelial cells) gained epithelial cell-like   
   properties when PIP2 was produced in their plasma membranes." says   
   Dr. Nakamura, with a look of excitement. The group was also able to   
   show that PIP2regulates these epithelial properties by recruiting Par3   
   -- a protein which guides vesicles intracellularly -- to the plasma   
   membrane. Once in the plasma membrane, Par3 facilitates the formation   
   of adherens junctions (one of the cellular junctions discussed above)   
   which anchor neighboring cells together. This partially prevents EMT,   
   and hence, progression of cancer.   
      
   "So," Dr. Nakamura explains, "In theory, PIP2's partial inhibition of   
   EMT could halt cancer progression, making this phospholipid an attractive   
   target molecule for anti-cancer treatment."  TUS' research has opened a   
   new avenue for the development of anti-cancer drug development, possibly   
   giving us a solution that will "stick."   
      
   ==========================================================================   
   Story Source: Materials provided by Tokyo_University_of_Science. Note:   
   Content may be edited for style and length.   
      
      
   ==========================================================================   
   Journal Reference:   
      1. Kaori Kanemaru, Makoto Shimozawa, Manabu Kitamata, Rikuto Furuishi,   
         Hinako Kayano, Yui Sukawa, Yuuki Chiba, Takatsugu Fukuyama, Junya   
         Hasegawa, Hiroki Nakanishi, Takuma Kishimoto, Kazuya Tsujita,   
         Kazuma Tanaka, Toshiki Itoh, Junko Sasaki, Takehiko Sasaki, Kiyoko   
         Fukami, Yoshikazu Nakamura. Plasma membrane phosphatidylinositol   
         (4,5)- bisphosphate is critical for determination of epithelial   
         characteristics.   
      
         Nature Communications, 2022; 13 (1) DOI: 10.1038/s41467-022-30061-9   
   ==========================================================================   
      
   Link to news story:   
   https://www.sciencedaily.com/releases/2022/05/220509100934.htm   
      
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