Tamoxifen overrides autophagy inhibition in Beclin-1-deficient glioma cells and their resistance to adenovirus-mediated oncolysis via upregulation...
Kaverina N. V., Kadagidze Z. G., Borovjagin A. V., Karseladze A. I., Kim C. K., Lesniak M. S., Miska J., Zhang P., Baryshnikova M. A., Xiao T., Ornelles D., Cobbs C., Khramtsov A., Ulasov I. V.
Oncogene
Vol.37, Issue46, P. 6069-6082
Опубликовано: 2018
Тип ресурса: Статья
DOI:10.1038/s41388-018-0395-9
Аннотация:
Autophagy is an evolutionarily conserved process regulating cellular homeostasis via digestion of dysfunctional proteins and whole cellular organelles by mechanisms, involving their enclosure into double-membrane vacuoles that are subsequently fused to lysosomes. Glioma stem cells utilize autophagy as a main mechanism of cell survival and stress response. Most recently, we and others demonstrated induction of autophagy in gliomas in response to treatment with chemical drugs, such as temozolomide (TMZ) or oncolytic adenoviruses (Ads). As autophagy has been implicated in the mechanism of Ad-mediated cell killing, autophagy deficiency in some glioma tumors could be the reason for their resistance to oncolysis. Despite the observed connection, the exact relationship between autophagy-activating cell signaling and adenoviral infection remains unclear. Here, we report that inhibition of autophagy in target glioma cells induces their resistance to killing by oncolytic agent CRAd-S-5/3. Furthe
Ключевые слова:
3 methyladenine; bafilomycin A1; beclin 1; conditionally replicating adenovirus; protein Bax; protein p53; PUMA protein; tamoxifen; apoptosis regulatory protein; Bax protein, mouse; BBC3 protein, human; beclin 1; oncoprotein; protein Bax; tamoxifen; A-549 cell line; animal experiment; animal model; antiproliferative activity; apoptosis; Article; autophagy; BAX gene; cancer resistance; cell aging; cell death; cell killing; cell viability; cohort analysis; controlled study; DNA damage; down regulation; drug cytotoxicity; drug mechanism; drug sensitivity; female; gene expression regulation; glioma; glioma cell; human; human cell; in vitro study; mouse; nonhuman; oncolytic virotherapy; priority journal; PUMA gene; signal transduction; U-118MG cell line; U-251MG cell line; U-87MG ATCC cell line; upregulation; Adenoviridae; animal; autophagy; brain tumor; cell line; cell proliferation; cell survival; drug effect; genetics; HEK293 cell line; oncolytic virotherapy; procedures; tumor cell line
Язык текста: Английский
ISSN: 1476-5594
Kaverina N. V.
Kadagidze Z. G.
Borovjagin A. V.
Karseladze A. I.
Kim C. K.
Lesniak M. S.
Miska J.
Zhang P.
Baryshnikova M. A.
Xiao T.
Ornelles D.
Cobbs C.
Khramtsov A.
Ulasov I. V. Il`ya Valentinovich 1975-
Каверина Н. В.
Кадагидзе З. Г.
Боровйагин А. В.
Карселадзе А. И.
Ким C. К.
Лесниак М. С.
Миска Й.
Жанг П.
Барyшникова М. А.
Хиао Т.
Орнеллес Д.
Cоббс C.
Храмцов А.
Уласов И. В. Илья Валентинович 1975-
Tamoxifen overrides autophagy inhibition in Beclin-1-deficient glioma cells and their resistance to adenovirus-mediated oncolysis via upregulation of PUMA and BAX
Tamoxifen overrides autophagy inhibition in Beclin-1-deficient glioma cells and their resistance to adenovirus-mediated oncolysis via upregulation...
Текст визуальный непосредственный
Oncogene
Nature Publishing Group
Vol.37, Issue46 P. 6069-6082
2018
Статья
3 methyladenine bafilomycin A1 beclin 1 conditionally replicating adenovirus protein Bax protein p53 PUMA protein tamoxifen apoptosis regulatory protein Bax protein, mouse BBC3 protein, human beclin 1 oncoprotein protein Bax tamoxifen A-549 cell line animal experiment animal model antiproliferative activity apoptosis Article autophagy BAX gene cancer resistance cell aging cell death cell killing cell viability cohort analysis controlled study DNA damage down regulation drug cytotoxicity drug mechanism drug sensitivity female gene expression regulation glioma glioma cell human human cell in vitro study mouse nonhuman oncolytic virotherapy priority journal PUMA gene signal transduction U-118MG cell line U-251MG cell line U-87MG ATCC cell line upregulation Adenoviridae animal autophagy brain tumor cell line cell proliferation cell survival drug effect genetics HEK293 cell line oncolytic virotherapy procedures tumor cell line
Autophagy is an evolutionarily conserved process regulating cellular homeostasis via digestion of dysfunctional proteins and whole cellular organelles by mechanisms, involving their enclosure into double-membrane vacuoles that are subsequently fused to lysosomes. Glioma stem cells utilize autophagy as a main mechanism of cell survival and stress response. Most recently, we and others demonstrated induction of autophagy in gliomas in response to treatment with chemical drugs, such as temozolomide (TMZ) or oncolytic adenoviruses (Ads). As autophagy has been implicated in the mechanism of Ad-mediated cell killing, autophagy deficiency in some glioma tumors could be the reason for their resistance to oncolysis. Despite the observed connection, the exact relationship between autophagy-activating cell signaling and adenoviral infection remains unclear. Here, we report that inhibition of autophagy in target glioma cells induces their resistance to killing by oncolytic agent CRAd-S-5/3. Furthe