Regulation of eIF4F Translation Initiation Complex by the Peptidyl Prolyl Isomerase FKBP7 in Taxane-resistant Prostate Cancer
Purpose: Targeted therapies that use the signaling path-characterize the function of human FKBP7 and explore its ways involved in prostate cancer are required to overcome role in cancer. We discovered that FKBP7 was upregulated chemoresistance and improve treatment outcomes for men. in human prostat...
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2019
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paper:paper_10780432_v25_n2_p710_Garrido2023-06-08T16:05:33Z Regulation of eIF4F Translation Initiation Complex by the Peptidyl Prolyl Isomerase FKBP7 in Taxane-resistant Prostate Cancer cabazitaxel docetaxel initiation factor 4F initiation factor 4FG peptidylprolyl isomerase peptidylprolyl isomerase FKBP7 short hairpin RNA small interfering RNA taxane derivative unclassified drug animal experiment animal model animal tissue Article cancer resistance carcinogenicity cell proliferation cell survival controlled study drug targeting enzyme activity gene expression regulation gene knockdown gene silencing genetic transfection human human cell human tissue in vitro study in vivo study intracellular signaling male mass spectrometry nonhuman priority journal prostate cancer cell line protein expression protein protein interaction tissue microarray translation initiation translation regulation tumor xenograft upregulation Purpose: Targeted therapies that use the signaling path-characterize the function of human FKBP7 and explore its ways involved in prostate cancer are required to overcome role in cancer. We discovered that FKBP7 was upregulated chemoresistance and improve treatment outcomes for men. in human prostate cancers and its expression correlated Molecular chaperones play a key role in the regulation of with the recurrence observed in patients receiving doce-protein homeostasis and are potential targets for overcom-taxel. FKBP7 silencing showed that FKBP7 is required to ing chemoresistance. maintain the growth of chemoresistant cell lines and Experimental Design: We established 4 chemoresistant chemoresistant tumors in mice. Mass spectrometry analysis prostate cancer cell lines and used image-based high-content revealed that FKBP7 interacts with eIF4G, a component of siRNA functional screening, based on gene-expression signa-the eIF4F translation initiation complex, to mediate the ture, to explore mechanisms of chemoresistance and identify survival of chemoresistant cells. Using small-molecule new potential targets with potential roles in taxane resistance. inhibitors of eIF4A, the RNA helicase component of The functional role of a new target was assessed by in vitro and eIF4F, we were able to kill docetaxel- and cabazitaxel-in vivo silencing, and mass spectrometry analysis was used to resistant cells. identify its downstream effectors. Conclusions: Targeting FKBP7 or the eIF4G-containing Results: We identified FKBP7, a prolyl-peptidyl isomer-eIF4F translation initiation complex could be novel thera-ase overexpressed in docetaxel-resistant and in cabazitaxel-peutic strategies to eradicate taxane-resistant prostate cancer resistant prostate cancer cells. This is the first study to cells. © 2018 American Association for Cancer Research. 2019 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_10780432_v25_n2_p710_Garrido http://hdl.handle.net/20.500.12110/paper_10780432_v25_n2_p710_Garrido |
| institution |
Universidad de Buenos Aires |
| institution_str |
I-28 |
| repository_str |
R-134 |
| collection |
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
| topic |
cabazitaxel docetaxel initiation factor 4F initiation factor 4FG peptidylprolyl isomerase peptidylprolyl isomerase FKBP7 short hairpin RNA small interfering RNA taxane derivative unclassified drug animal experiment animal model animal tissue Article cancer resistance carcinogenicity cell proliferation cell survival controlled study drug targeting enzyme activity gene expression regulation gene knockdown gene silencing genetic transfection human human cell human tissue in vitro study in vivo study intracellular signaling male mass spectrometry nonhuman priority journal prostate cancer cell line protein expression protein protein interaction tissue microarray translation initiation translation regulation tumor xenograft upregulation |
| spellingShingle |
cabazitaxel docetaxel initiation factor 4F initiation factor 4FG peptidylprolyl isomerase peptidylprolyl isomerase FKBP7 short hairpin RNA small interfering RNA taxane derivative unclassified drug animal experiment animal model animal tissue Article cancer resistance carcinogenicity cell proliferation cell survival controlled study drug targeting enzyme activity gene expression regulation gene knockdown gene silencing genetic transfection human human cell human tissue in vitro study in vivo study intracellular signaling male mass spectrometry nonhuman priority journal prostate cancer cell line protein expression protein protein interaction tissue microarray translation initiation translation regulation tumor xenograft upregulation Regulation of eIF4F Translation Initiation Complex by the Peptidyl Prolyl Isomerase FKBP7 in Taxane-resistant Prostate Cancer |
| topic_facet |
cabazitaxel docetaxel initiation factor 4F initiation factor 4FG peptidylprolyl isomerase peptidylprolyl isomerase FKBP7 short hairpin RNA small interfering RNA taxane derivative unclassified drug animal experiment animal model animal tissue Article cancer resistance carcinogenicity cell proliferation cell survival controlled study drug targeting enzyme activity gene expression regulation gene knockdown gene silencing genetic transfection human human cell human tissue in vitro study in vivo study intracellular signaling male mass spectrometry nonhuman priority journal prostate cancer cell line protein expression protein protein interaction tissue microarray translation initiation translation regulation tumor xenograft upregulation |
| description |
Purpose: Targeted therapies that use the signaling path-characterize the function of human FKBP7 and explore its ways involved in prostate cancer are required to overcome role in cancer. We discovered that FKBP7 was upregulated chemoresistance and improve treatment outcomes for men. in human prostate cancers and its expression correlated Molecular chaperones play a key role in the regulation of with the recurrence observed in patients receiving doce-protein homeostasis and are potential targets for overcom-taxel. FKBP7 silencing showed that FKBP7 is required to ing chemoresistance. maintain the growth of chemoresistant cell lines and Experimental Design: We established 4 chemoresistant chemoresistant tumors in mice. Mass spectrometry analysis prostate cancer cell lines and used image-based high-content revealed that FKBP7 interacts with eIF4G, a component of siRNA functional screening, based on gene-expression signa-the eIF4F translation initiation complex, to mediate the ture, to explore mechanisms of chemoresistance and identify survival of chemoresistant cells. Using small-molecule new potential targets with potential roles in taxane resistance. inhibitors of eIF4A, the RNA helicase component of The functional role of a new target was assessed by in vitro and eIF4F, we were able to kill docetaxel- and cabazitaxel-in vivo silencing, and mass spectrometry analysis was used to resistant cells. identify its downstream effectors. Conclusions: Targeting FKBP7 or the eIF4G-containing Results: We identified FKBP7, a prolyl-peptidyl isomer-eIF4F translation initiation complex could be novel thera-ase overexpressed in docetaxel-resistant and in cabazitaxel-peutic strategies to eradicate taxane-resistant prostate cancer resistant prostate cancer cells. This is the first study to cells. © 2018 American Association for Cancer Research. |
| title |
Regulation of eIF4F Translation Initiation Complex by the Peptidyl Prolyl Isomerase FKBP7 in Taxane-resistant Prostate Cancer |
| title_short |
Regulation of eIF4F Translation Initiation Complex by the Peptidyl Prolyl Isomerase FKBP7 in Taxane-resistant Prostate Cancer |
| title_full |
Regulation of eIF4F Translation Initiation Complex by the Peptidyl Prolyl Isomerase FKBP7 in Taxane-resistant Prostate Cancer |
| title_fullStr |
Regulation of eIF4F Translation Initiation Complex by the Peptidyl Prolyl Isomerase FKBP7 in Taxane-resistant Prostate Cancer |
| title_full_unstemmed |
Regulation of eIF4F Translation Initiation Complex by the Peptidyl Prolyl Isomerase FKBP7 in Taxane-resistant Prostate Cancer |
| title_sort |
regulation of eif4f translation initiation complex by the peptidyl prolyl isomerase fkbp7 in taxane-resistant prostate cancer |
| publishDate |
2019 |
| url |
https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_10780432_v25_n2_p710_Garrido http://hdl.handle.net/20.500.12110/paper_10780432_v25_n2_p710_Garrido |
| _version_ |
1768545843377340416 |