HAGA HisashiProfessor
- Laboratory
- Laboratory of Cell Dynamics
- Research Theme
- Collective Behavior and 3D Morphogenesis of Epithelial Cells, Cancer Cell Invasion
- Research Keywords
collective cell movement, 3D morphogenesis, cancer cell invasion
Overview of Research
■3D morphogenesis of epithelial sheets using viscoelastic substrates
3D morphogenesis is an essential process for various phenomena such as embryonic development and tissue formation. Mechanical properties of the extracellular matrix are understood as factors that affect the cell behavior. We show that a collagen gel overlay induced epithelial sheet folding from the periphery that migrated inwardly, resulting in the formation of a 3D luminal structure in a collagen gel. We also cultured epithelial cells on a viscous substrate. The cells presented a tulip hat-like 3D morphology induced by the deformation of the peripheral substrate.
■Acceleration of metastatic growth of cancer cells induced by substrate stiffness
Recent studies have shown that stiff substrates trigger cancer progression such as metastasis and cell proliferation. For example, it is well known that malignant breast tissues are stiff compared with normal mammary tissues. We found that stiff substrates enhanced cancer progression by upregulating matrix metalloproteinase-7 expression, which is an indicator of poor prognosis, through the positive feedback loop of yes-associated protein, epidermal growth factor receptor, integrin and myosin regulatory light chain in colorectal cancer.
Charge
- School of Science:
Biological Science course (Macromolecular Functions), Core Laboratories - Graduate School of Life Science:
Division of Soft Matter, Soft Matter Biophysics
Representative Publications
K. Onishi, S. Ishihara, M. Takahashi, A. Sakai, A. Enomoto, K. Suzuki, and H. Haga: Substrate stiffness induces nuclear localization of myosin regulatory light chain to suppress apoptosis, FEBS Letters, 597, 643-656 (2023).
S. Ishihara, H. Kurosawa, and H. Haga: Stiffness-Modulation of Collagen Gels by Genipin-Crosslinking for Cell Culture, Gels, 9, 148 (2023).
S. Ishida-Ishihara, R. Takada, K. Furusawa, S. Ishihara, and H. Haga: Improvement of the cell viability of hepatocytes cultured in three-dimensional collagen gels using pump-free perfusion driven by water level difference, Scientific Reports, 12, 20269, 1-11 (2022).
Y. Kumagai, J. Nio-Kobayashi, S. Ishihara, A. Enomoto, M. Akiyama, R. Ichihara, and H. Haga: The Interferon-β/STAT1 Axis Drives the Collective Invasion of Skin Squamous Cell Carcinoma with Sealed Intercellular Spaces, Oncogenesis, 11, 27 (2022).
H. Oyama, A. Nukuda, S. Ishihara, and H. Haga: Soft Surfaces Promote Astrocytic Differentiation of Mouse Embryonic Neural Stem Cells via Dephosphorylation of MRLC in the Absence of Serum, Scientific Reports, 11, 19574, 1-11 (2021).
S. Ishida-Ishihara, M. Akiyama, K. Furusawa, I. Naguro, H. Ryuno, T. Sushida, S. Ishihara, and H. Haga: Osmotic Gradients Induce Stable Dome Morphogenesis on Extracellular Matrix, Journal of Cell Science, 133, jcs243865 (2020).
Y. Kumagai, J. Nio-Kobayashi, S. Ishida-Ishihara, H. Tachibana, R. Omori, A. Enomoto, S. Ishihara, and H. Haga: The intercellular expression of type-XVII collagen, laminin-332, and integrin-β1 promote contact following during the collective invasion of a cancer cell population, Biochem. Biophys. Res. Commun., 514, 1115-1121 (2019).
Refer to HOKKAIDO UNIVERSITY RESEARCHERS DIRECTORY
(https://researchers.general.hokudai.ac.jp/profile/en.K6kRFVurrafZ9RWNSKrWFw==.html)
Note
<Office Hour>
– Time: Anytime during the lecture period
– Place: Science Bldg. No.2, 6F, #2-612
Please contact in advance by E-mail.
E-mail: haga[at]sci.hokudai.ac.jp
Affiliation
- Faculty of Advanced Life Science, Department of Advanced Transdisciplinary Sciences, Cellular Dynamics Science
- Frontier Research Center for Advanced Material and Life Science, Global Collaboration Unit, Soft Matter Collaborative Research Unit