2022 Fiscal Year Final Research Report
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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| 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 |
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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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| Free Research Field |
細胞生物学
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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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