Identifying the Interactions That Drive Cell Migration in Brain Cancer

Ikoma, Japan—Ever wondered how the different cells in our body communicate with each other to fulfill their different roles—be it cells repairing a tissue injury or immune cells moving towards an invading pathogen (microorganisms that causes disease) to engulf it? To move forward or migrate, cells must exert forces or interact with their surrounding environment. Interestingly, however, a fault in these interactions can also be the reason for spread of deadly cancer cells, such as in glioblastoma or brain tumor. While the importance of these interactions is well-understood, the machinery involved in these interactions at the molecular level remains a mystery.

Now, a team of researchers led by Professor Naoyuki Inagaki from Nara Institute of Science and Technology, Japan, along with Dr. Yonehiro Kanemura from NHO Osaka National Hospital, Japan; Dr. Tatsuo Kinashi from Kansai Medical University, Japan; and Dr. Daisuke Kawauchi from Nagoya City University, Japan, has identified the underlying mechanism involving a protein called shootin1b that promotes cell migration or movement in glioblastoma. The study was published online in Advanced Science on August 13, 2025.

“We discovered that an abnormal activity of shootin1b promotes the movement of cancer cells and spread of glioblastoma, the most common and difficult to treat brain tumor in adults,” explains Professor Inagaki.

Notably, the study sheds light on a newly discovered molecular interaction that drives rapid migration of dendritic cells, a type of immune cell that capture pathogens. Migrating dendritic cells need to exert backward forces onto the environment to propel themselves forward. In addition, different environmental cues in the form of chemoattractants (molecules that attract moving cells), regulate their speed and direction. At the front of migrating cells, intracellular actin (a protein that generates force and movement in the cell) filaments polymerize, generating a backward flow of actin.

Shootin1b forms clutches that links the cell’s internal actin to external environment through adhesive molecules, converting this backward actin movement into traction force that propels the cell forward. This adhesion–clutch system mediates cell movement depending on the chemoattractant force. Shootin1b and the adhesion molecule transmit weak traction forces which is well-suited for rapid cell migration, presenting a potential target for preventing spread of glioblastoma.

“By suppressing the abnormal activity of shootin1b, we can prevent the migration of glioblastoma cells and spread of cancer. Thus, shootin1b could be a novel therapeutic target for glioblastoma,” says Professor Inagaki.  To put these findings into context, glioblastoma has a five year survival rate of only 5%, and the targeted suppression of glioblastoma invasion by inhibiting the abnormal activity of shootin1b could bring a ray of hope in the lives of many. Thus, these findings can pave the way for the development of new treatment strategies for this highly intractable cancer.  

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Resource

Title: Weak and Tunable Adhesion–Clutch Drives Rapid Cell Migration and Glioblastoma Invasion

Authors: Kentarou Baba, Ami Fukushi-Kumagai, Megumi Morisaki, Ryosuke Takeuchi, Zhize Xiao, Yoshikazu Nagashima, Mizuki Sakai, Yasuna Higashiguchi, Hiroko Katsuno-Kambe, Asako Katsuma, Yoshihiro Ueda, Yuji Kamioka, Daisuke Kawauchi, Tatsuo Kinashi, Yonehiro Kanemura, and Naoyuki Inagaki

Journal: Advanced Science

DOI: 10.1002/advs.202502074

Information about the Laboratory of Systems Neurobiology and Medicine can be found at the following website: https://bsw3.naist.jp/inagaki/english/

About Nara Institute of Science and Technology (NAIST)

Established in 1991, Nara Institute of Science and Technology (NAIST) is a national university located in Kansai Science City, Japan. In 2018, NAIST underwent an organizational transformation to promote and continue interdisciplinary research in the fields of biological sciences, materials science, and information science. Known as one of the most prestigious research institutions in Japan, NAIST lays a strong emphasis on integrated research and collaborative co-creation with diverse stakeholders. NAIST envisions conducting cutting-edge research in frontier areas and training students to become tomorrow's leaders in science and technology.