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Analyzing the Function of Small GTPases by Microinjection of Plasmids into Polarized Epithelial Cells
Published on: May 31, 2011
Plectin is a novel regulator for apical extrusion of RasV12-transformed cells
Ailijiang Kadeer1,2, Takeshi Maruyama1,3, Mihoko Kajita1,3
1Division of Molecular Oncology, Institute for Genetic Medicine, Hokkaido University, Sapporo 060-0815, Japan.
Abstract:
Several lines of evidence have revealed that newly emerging transformed cells are often eliminated from the epithelium, though the underlying molecular mechanisms of this cancer preventive phenomenon still remain elusive. In this study, using mammalian cell culture systems we have identified plectin, a versatile cytoskeletal linker protein, as a novel regulator for apical extrusion of RasV12-transformed cells. Plectin is accumulated in RasV12 cells when they are surrounded by normal epithelial cells. Similarly, cytoskeletal proteins tubulin, keratin, and Epithelial Protein Lost In Neoplasm (EPLIN) are also accumulated in the transformed cells surrounded by normal cells. Knockdown or functional disruption of one of these molecules diminishes the accumulation of the others, indicating that the accumulation process of the individual protein mutually depends on each other. Furthermore, plectin-knockdown attenuates caveolin-1 (Cav-1) enrichment and PKA activity in RasV12 cells and profoundly suppresses the apical extrusion. These results indicate that the plectin-microtubules-EPLIN complex positively regulates apical elimination of RasV12-transformed cells from the epithelium in a coordinated fashion. Further development of this study would open a new avenue for cancer preventive medicine.
Insights
Plectin, a cytoskeletal protein, regulates the elimination of transformed cells from epithelia. This discovery offers new insights into cancer prevention mechanisms involving cell extrusion.
Area of Science:
- Cell Biology
- Cancer Research
- Biochemistry
Background:
- Emerging evidence suggests transformed cells are eliminated from epithelia, a cancer preventive mechanism.
- The molecular underpinnings of this epithelial cell extrusion remain largely unknown.
Purpose of the Study:
- To identify molecular regulators of apical extrusion of transformed cells.
- To elucidate the role of plectin in this cancer preventive process.
Main Methods:
- Mammalian cell culture systems were employed.
- Plectin and associated cytoskeletal proteins (tubulin, keratin, EPLIN) were analyzed in RasV12-transformed cells.
- Knockdown and functional disruption experiments were performed.
- Caveolin-1 (Cav-1) enrichment and PKA activity were assessed.
Main Results:
- Plectin accumulates in RasV12-transformed cells surrounded by normal epithelial cells.
- Accumulation of tubulin, keratin, and Epithelial Protein Lost In Neoplasm (EPLIN) is interdependent with plectin.
- Plectin knockdown reduces Cav-1 enrichment and PKA activity, suppressing apical extrusion.
- A plectin-microtubules-EPLIN complex regulates apical elimination of transformed cells.
Conclusions:
- Plectin is a novel regulator of apical extrusion of transformed epithelial cells.
- The plectin-microtubules-EPLIN complex plays a crucial role in eliminating cancer-prone cells.
- This research opens new avenues for developing cancer preventive strategies.
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