Ultrastructural analysis of the interaction between normal and transformed cells.
| Project/Area Number |
20K07559
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 50010:Tumor biology-related
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| Research Institution | Hokkaido University |
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Principal Investigator |
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| Project Period (FY) |
2020-04-01 – 2023-03-31
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| Project Status |
Completed (Fiscal Year 2022)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2022: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2021: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | 細胞競合 / RasV12 / 細胞膜 / 細胞突起 / 細胞間接着 / BARファミリータンパク質 / SrcY527F / Ras変異細胞 / 電子顕微鏡 / 超解像顕微鏡 |
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| Outline of Research at the Start |
がんの超初期段階において上皮細胞層に変異が生じると、変異細胞が上皮細胞層から積極的に体外へ排除される。この現象は、二つの過程に分けることができる。第一に、上皮細胞層に生じた変異細胞の自律的変化を隣接する正常細胞が受容する過程と、第二に、正常細胞が受容したシグナルが引き金となり、正常細胞が変異細胞を排除するための細胞非自律的な反応が起きる過程である。本研究では、これらの過程を制御する分子・形態メカニズムに迫る。
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| Outline of Final Research Achievements |
At the initial stage of carcinogenesis, RasV12-transformed cells surrounded by normal cells are apically extruded from the epithelium. However, the underlying mechanisms of this tumor-suppressive process still remain enigmatic. We first show by electron microscopic analysis that characteristic finger-like protrusions are projected from both normal and RasV12 cells at their interface. In addition, FBP17 accumulates in RasV12 cells, as well as surrounding normal cells, which plays a positive role in the formation of finger-like protrusions and apical elimination of RasV12 cells. Furthermore, cdc42 acts upstream of these processes. These results suggest that the cdc42/FBP17 pathway is a crucial trigger of cell competition, inducing 'protrusion to protrusion response’ between normal and RasV12-transformed cells.
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| Academic Significance and Societal Importance of the Research Achievements |
悪性腫瘍多くは、複数のがん遺伝子あるいはがん抑制遺伝子の変異が蓄積することによってがん化が進展していく。一方、がんの始まりは上皮細胞層の1個ないし数個の細胞に変異が生じることが要因とな る。これまでに、変異細胞と直接それを取り囲む正常上皮細胞間で何が起こるかについて、まだ殆ど分かっておらず、また、これらの病変を検出する方法もないことから、病理診断および臨床治療の対象外となっている。本研究において、変異細胞に隣接する正常細胞が特異的に細胞膜の形態および動態を制御する分子メカニズムが明らかになったことにより、超早期がん病変の診断法およびがんの予防的治療薬の開発に繋がると考えられる。
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Report
(4 results)
Research Products
(14 results)
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[Journal Article] Calcium sparks enhance the tissue fluidity within epithelial layers and promote apical extrusion of transformed cells2022
Author(s)
Kuromiya K, Aoki K, Ishibashi K, Yotabun M, Sekai M, Tanimura N, Iijima S, Ishikawa S, Kamasaki T, Akieda Y, Ishitani T, Hayashi T, Toda S, Yokoyama K, Lee CG, Usami I, Inoue H, Takigawa I, Gauquelin E, Sugimura K, Hino N, Fujita Y
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Journal Title
Cell Reports
Volume: 40
Issue: 2
Pages: 111078-111078
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] The CD44/COL17A1 Pathway Plays a Vital Role in the Formation of Multilayered, Transformed Epithelia.2021
Author(s)
Kozawa K, ,Sekai M, Ohba K, Ito S, Sako H, Maruyama T, Kakeno M , Kuromiya K, Kamasaki T, Kohashi K, Ishikawa S, Sato N, Asano S, Suzuki H, Tanimura N, Mukai Y, Gotoh N, Tanino M, Tanaka S Natsuga K, Soga T. Nakamura T, Yabuta Y, Saitou M, Ito T, Matsuura K, Tsunoda M,et.al..
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Journal Title
Curr Biol
Volume: 31
Issue: 14
Pages: 3086-3097
DOI
Related Report
Peer Reviewed / Open Access
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