Павел Копнин - Academia.edu (original) (raw)
Papers by Павел Копнин
Biochemistry (Moscow), 2019
Actin plays an important role in cellular adhesion, muscle and non-muscle contractility, migratio... more Actin plays an important role in cellular adhesion, muscle and non-muscle contractility, migration, polarization, mitosis, and meiosis. Investigation of specific mechanisms underlying these processes is essential not only for fundamental research but also for clinical applications, since modulations of actin isoforms are directly or indirectly correlate with severe pathologies. In this review we summarize the isoform-specific functions of actin associated with adhesion structures, motility and division of normal and tumor cells; alterations of the expression and structural organization of actin isoforms in normal and tumor cells. Selective regulation of cytoplasmic β- or γ-actin expression determines functional diversity between isoforms: β-actin plays the predominant role in contraction and intercellular adhesion, and γ-actin is responsible for the cellular plasticity and motility. Similar data were obtained in different epithelial and mesenchymal neoplastic cell cultures, as well as in immunomorphological comparison of normal human tissues with tumor analogues. Reorganization of the actin cytoskeleton and cell–cell contacts is essential for proliferation control and acquisition of invasiveness in epithelial tumors.
Advances in molecular oncology, 2017
Arkhiv patologii, 2017
Опухолевая прогрессия-это комплексный процесс, который затрагивает в том числе перестройку актино... more Опухолевая прогрессия-это комплексный процесс, который затрагивает в том числе перестройку актинового цитоскелета и ослабление адгезионных межклеточных контактов за счет прохождения опухолевыми клетками эпителиальномезенхимального перехода (ЭМП). Цель исследования-выявление корреляций между клиническими характеристиками, уровнем риска прогрессии и/или рецидивирования аденокарцином толстой кишки (АТК) человека и опухолевыми маркерами, ассоциированными с ЭМП. Материал и методы. Проведено иммуногистохимическое исследование образцов аденокарцином нисходящей ободочной и сигмовидной кишки. Срезы фиксированных формалином парафинизированных блоков инкубировали с антигенспецифичными антителами, затем вторичными антителами, меченными флюорохромами, и проводили анализ интенсивности флюоресценции полученных при микроскопии изображений. Результаты. В опухолевых клетках по сравнению с нормальной тканью толстой кишки наблюдалось слабое окрашивание Е-кадгерина в зонах межклеточных контактов. Снижение мембранной окраски и ядерная локализация β-катенина детектировались в умеренно дифференцированных G2-опухолях и низкодифференцированных G3-опухолях. Значимое снижение количества β-актина наблюдалось практически во всех опухолевых образцах, а увеличение количества γ-актина-в основном в образцах, относящихся к IV стадии заболевания. Заключение. Выявлена связь между стадией, дифференцировочным статусом опухоли, риском развития рецидива или прогрессией заболевания и нарушениями экспрессии различных маркеров ЭМП: полная или частичная потеря экспрессии Е-кадгерина и реорганизация β-катенина в межклеточных контактах, а также изменение соотношения цитоплазматических изоформ актина на поздних стадиях развития АТК. Мы полагаем, что данные молекулярные маркеры могут обладать прогностическим потенциалом. Ключевые слова: эпителиально-мезенхимальный переход, цитоплазматические изоформы актина, аденокарцинома толстой кишки, Е-кадгерин, β-катенин. A change in the expression of membrane-associated proteins and cytoplasmic actin isoforms in the progression of human colon tumors
Oncotarget, 2016
Actin microfilaments and microtubules are both highly dynamic cytoskeleton components implicated ... more Actin microfilaments and microtubules are both highly dynamic cytoskeleton components implicated in a wide range of intracellular processes as well as cellcell and cell-substrate interactions. The interactions of actin filaments with the microtubule system play an important role in the assembly and maintenance of 3D cell structure. Here we demonstrate that cytoplasmic actins are differentially distributed in relation to the microtubule system. LSM, 3D-SIM, proximity ligation assay (PLA) and co-immunoprecipitation methods applied in combination with selective depletion of β-or γ-cytoplasmic actins revealed a selective interaction between microtubules and γ-, but not β-cytoplasmic actin via the microtubule +TIPs protein EB1. EB1-positive comet distribution analysis and quantification have shown more effective microtubule growth in the absence of β-actin. Our data represent the first demonstration that microtubule +TIPs protein EB1 interacts mainly with γ-cytoplasmic actin in epithelial cells.
Oncotarget, Jan 10, 2015
Here we have shown that β-cytoplasmic actin acts as a tumor suppressor, inhibiting cell growth an... more Here we have shown that β-cytoplasmic actin acts as a tumor suppressor, inhibiting cell growth and invasion in vitro and tumor growth in vivo. In contrast, γ-cytoplasmic actin increases the oncogenic potential via ERK1/2, p34-Arc, WAVE2, cofilin1, PP1 and other regulatory proteins. There is a positive feedback loop between γ-actin expression and ERK1/2 activation. We conclude that non-muscle actin isoforms should not be considered as merely housekeeping proteins and the β/γ-actins ratio can be used as an oncogenic marker at least for lung and colon carcinomas. Agents that increase β- and/or decrease γ-actin expression may be useful for anticancer therapy.
Oncotarget, 2015
Actin microfilaments and microtubules are both highly dynamic cytoskeleton components implicated ... more Actin microfilaments and microtubules are both highly dynamic cytoskeleton components implicated in a wide range of intracellular processes as well as cellcell and cell-substrate interactions. The interactions of actin filaments with the microtubule system play an important role in the assembly and maintenance of 3D cell structure. Here we demonstrate that cytoplasmic actins are differentially distributed in relation to the microtubule system. LSM, 3D-SIM, proximity ligation assay (PLA) and co-immunoprecipitation methods applied in combination with selective depletion of β-or γ-cytoplasmic actins revealed a selective interaction between microtubules and γ-, but not β-cytoplasmic actin via the microtubule +TIPs protein EB1. EB1-positive comet distribution analysis and quantification have shown more effective microtubule growth in the absence of β-actin. Our data represent the first demonstration that microtubule +TIPs protein EB1 interacts mainly with γ-cytoplasmic actin in epithelial cells.
Advances in molecular oncology
Oncotarget, Jan 10, 2015
Here we have shown that β-cytoplasmic actin acts as a tumor suppressor, inhibiting cell growth an... more Here we have shown that β-cytoplasmic actin acts as a tumor suppressor, inhibiting cell growth and invasion in vitro and tumor growth in vivo. In contrast, γ-cytoplasmic actin increases the oncogenic potential via ERK1/2, p34-Arc, WAVE2, cofilin1, PP1 and other regulatory proteins. There is a positive feedback loop between γ-actin expression and ERK1/2 activation. We conclude that non-muscle actin isoforms should not be considered as merely housekeeping proteins and the β/γ-actins ratio can be used as an oncogenic marker at least for lung and colon carcinomas. Agents that increase β- and/or decrease γ-actin expression may be useful for anticancer therapy.
Biochemistry (Moscow), 2019
Actin plays an important role in cellular adhesion, muscle and non-muscle contractility, migratio... more Actin plays an important role in cellular adhesion, muscle and non-muscle contractility, migration, polarization, mitosis, and meiosis. Investigation of specific mechanisms underlying these processes is essential not only for fundamental research but also for clinical applications, since modulations of actin isoforms are directly or indirectly correlate with severe pathologies. In this review we summarize the isoform-specific functions of actin associated with adhesion structures, motility and division of normal and tumor cells; alterations of the expression and structural organization of actin isoforms in normal and tumor cells. Selective regulation of cytoplasmic β- or γ-actin expression determines functional diversity between isoforms: β-actin plays the predominant role in contraction and intercellular adhesion, and γ-actin is responsible for the cellular plasticity and motility. Similar data were obtained in different epithelial and mesenchymal neoplastic cell cultures, as well as in immunomorphological comparison of normal human tissues with tumor analogues. Reorganization of the actin cytoskeleton and cell–cell contacts is essential for proliferation control and acquisition of invasiveness in epithelial tumors.
Advances in molecular oncology, 2017
Arkhiv patologii, 2017
Опухолевая прогрессия-это комплексный процесс, который затрагивает в том числе перестройку актино... more Опухолевая прогрессия-это комплексный процесс, который затрагивает в том числе перестройку актинового цитоскелета и ослабление адгезионных межклеточных контактов за счет прохождения опухолевыми клетками эпителиальномезенхимального перехода (ЭМП). Цель исследования-выявление корреляций между клиническими характеристиками, уровнем риска прогрессии и/или рецидивирования аденокарцином толстой кишки (АТК) человека и опухолевыми маркерами, ассоциированными с ЭМП. Материал и методы. Проведено иммуногистохимическое исследование образцов аденокарцином нисходящей ободочной и сигмовидной кишки. Срезы фиксированных формалином парафинизированных блоков инкубировали с антигенспецифичными антителами, затем вторичными антителами, меченными флюорохромами, и проводили анализ интенсивности флюоресценции полученных при микроскопии изображений. Результаты. В опухолевых клетках по сравнению с нормальной тканью толстой кишки наблюдалось слабое окрашивание Е-кадгерина в зонах межклеточных контактов. Снижение мембранной окраски и ядерная локализация β-катенина детектировались в умеренно дифференцированных G2-опухолях и низкодифференцированных G3-опухолях. Значимое снижение количества β-актина наблюдалось практически во всех опухолевых образцах, а увеличение количества γ-актина-в основном в образцах, относящихся к IV стадии заболевания. Заключение. Выявлена связь между стадией, дифференцировочным статусом опухоли, риском развития рецидива или прогрессией заболевания и нарушениями экспрессии различных маркеров ЭМП: полная или частичная потеря экспрессии Е-кадгерина и реорганизация β-катенина в межклеточных контактах, а также изменение соотношения цитоплазматических изоформ актина на поздних стадиях развития АТК. Мы полагаем, что данные молекулярные маркеры могут обладать прогностическим потенциалом. Ключевые слова: эпителиально-мезенхимальный переход, цитоплазматические изоформы актина, аденокарцинома толстой кишки, Е-кадгерин, β-катенин. A change in the expression of membrane-associated proteins and cytoplasmic actin isoforms in the progression of human colon tumors
Oncotarget, 2016
Actin microfilaments and microtubules are both highly dynamic cytoskeleton components implicated ... more Actin microfilaments and microtubules are both highly dynamic cytoskeleton components implicated in a wide range of intracellular processes as well as cellcell and cell-substrate interactions. The interactions of actin filaments with the microtubule system play an important role in the assembly and maintenance of 3D cell structure. Here we demonstrate that cytoplasmic actins are differentially distributed in relation to the microtubule system. LSM, 3D-SIM, proximity ligation assay (PLA) and co-immunoprecipitation methods applied in combination with selective depletion of β-or γ-cytoplasmic actins revealed a selective interaction between microtubules and γ-, but not β-cytoplasmic actin via the microtubule +TIPs protein EB1. EB1-positive comet distribution analysis and quantification have shown more effective microtubule growth in the absence of β-actin. Our data represent the first demonstration that microtubule +TIPs protein EB1 interacts mainly with γ-cytoplasmic actin in epithelial cells.
Oncotarget, Jan 10, 2015
Here we have shown that β-cytoplasmic actin acts as a tumor suppressor, inhibiting cell growth an... more Here we have shown that β-cytoplasmic actin acts as a tumor suppressor, inhibiting cell growth and invasion in vitro and tumor growth in vivo. In contrast, γ-cytoplasmic actin increases the oncogenic potential via ERK1/2, p34-Arc, WAVE2, cofilin1, PP1 and other regulatory proteins. There is a positive feedback loop between γ-actin expression and ERK1/2 activation. We conclude that non-muscle actin isoforms should not be considered as merely housekeeping proteins and the β/γ-actins ratio can be used as an oncogenic marker at least for lung and colon carcinomas. Agents that increase β- and/or decrease γ-actin expression may be useful for anticancer therapy.
Oncotarget, 2015
Actin microfilaments and microtubules are both highly dynamic cytoskeleton components implicated ... more Actin microfilaments and microtubules are both highly dynamic cytoskeleton components implicated in a wide range of intracellular processes as well as cellcell and cell-substrate interactions. The interactions of actin filaments with the microtubule system play an important role in the assembly and maintenance of 3D cell structure. Here we demonstrate that cytoplasmic actins are differentially distributed in relation to the microtubule system. LSM, 3D-SIM, proximity ligation assay (PLA) and co-immunoprecipitation methods applied in combination with selective depletion of β-or γ-cytoplasmic actins revealed a selective interaction between microtubules and γ-, but not β-cytoplasmic actin via the microtubule +TIPs protein EB1. EB1-positive comet distribution analysis and quantification have shown more effective microtubule growth in the absence of β-actin. Our data represent the first demonstration that microtubule +TIPs protein EB1 interacts mainly with γ-cytoplasmic actin in epithelial cells.
Advances in molecular oncology
Oncotarget, Jan 10, 2015
Here we have shown that β-cytoplasmic actin acts as a tumor suppressor, inhibiting cell growth an... more Here we have shown that β-cytoplasmic actin acts as a tumor suppressor, inhibiting cell growth and invasion in vitro and tumor growth in vivo. In contrast, γ-cytoplasmic actin increases the oncogenic potential via ERK1/2, p34-Arc, WAVE2, cofilin1, PP1 and other regulatory proteins. There is a positive feedback loop between γ-actin expression and ERK1/2 activation. We conclude that non-muscle actin isoforms should not be considered as merely housekeeping proteins and the β/γ-actins ratio can be used as an oncogenic marker at least for lung and colon carcinomas. Agents that increase β- and/or decrease γ-actin expression may be useful for anticancer therapy.