Heme oxygenase-1 in the forefront of a multi-molecular network that governs cell-cell contacts and filopodia-induced zippering in prostate cancer
Prostate cancer (PCa) cells display abnormal expression of cytoskeletal proteins resulting in an augmented capacity to resist chemotherapy and colonize distant organs. We have previously shown that heme oxygenase 1 (HO-1) is implicated in cell morphology regulation in PCa. Here, through a multi ...
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2016
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| Acceso en línea: | https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_20414889_v7_n12_pe2570_Paez http://hdl.handle.net/20.500.12110/paper_20414889_v7_n12_pe2570_Paez |
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paper:paper_20414889_v7_n12_pe2570_Paez2023-06-08T16:33:10Z Heme oxygenase-1 in the forefront of a multi-molecular network that governs cell-cell contacts and filopodia-induced zippering in prostate cancer conditioned medium heme oxygenase 1 protein binding transcriptome animal cell communication cell motion coculture conditioned medium cytoskeleton DNA microarray drug effects enzymology gene expression regulation gene regulatory network genetics human male metabolism mouse pathology pharmacology prostate tumor proteomics pseudopodium sequence analysis tandem mass spectrometry tumor cell line X ray crystallography Animals Cell Communication Cell Line, Tumor Cell Movement Coculture Techniques Crystallography, X-Ray Culture Media, Conditioned Cytoskeleton Gene Expression Regulation, Neoplastic Gene Regulatory Networks Heme Oxygenase-1 Humans Male Mice Oligonucleotide Array Sequence Analysis Prostatic Neoplasms Protein Binding Proteomics Pseudopodia Sequence Analysis, RNA Tandem Mass Spectrometry Transcriptome Prostate cancer (PCa) cells display abnormal expression of cytoskeletal proteins resulting in an augmented capacity to resist chemotherapy and colonize distant organs. We have previously shown that heme oxygenase 1 (HO-1) is implicated in cell morphology regulation in PCa. Here, through a multi 'omics' approach we define the HO-1 interactome in PCa, identifying HO-1 molecular partners associated with the integrity of the cellular cytoskeleton. The bioinformatics screening for these cytoskeletal-related partners reveal that they are highly misregulated in prostate adenocarcinoma compared with normal prostate tissue. Under HO-1 induction, PCa cells present reduced frequency in migration events, trajectory and cell velocity and, a significant higher proportion of filopodia-like protrusions favoring zippering among neighboring cells. Moreover forced expression of HO-1 was also capable of altering cell protrusions in transwell co-culture systems of PCa cells with MC3T3 cells (pre-osteoblastic cell line). Accordingly, these effects were reversed under siHO. Transcriptomics profiling evidenced significant modulation of key markers related to cell adhesion and cell-cell communication under HO-1 induction. The integration from our omics-based research provides a four molecular pathway foundation (ANXA2/HMGA1/POU3F1; NFRSF13/GSN; TMOD3/RAI14/VWF; and PLAT/PLAU) behind HO-1 regulation of tumor cytoskeletal cell compartments. The complementary proteomics and transcriptomics approaches presented here promise to move us closer to unravel the molecular framework underpinning HO-1 involvement in the modulation of cytoskeleton pathways, pushing toward a less aggressive phenotype in PCa. 2016 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_20414889_v7_n12_pe2570_Paez http://hdl.handle.net/20.500.12110/paper_20414889_v7_n12_pe2570_Paez |
| institution |
Universidad de Buenos Aires |
| institution_str |
I-28 |
| repository_str |
R-134 |
| collection |
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
| topic |
conditioned medium heme oxygenase 1 protein binding transcriptome animal cell communication cell motion coculture conditioned medium cytoskeleton DNA microarray drug effects enzymology gene expression regulation gene regulatory network genetics human male metabolism mouse pathology pharmacology prostate tumor proteomics pseudopodium sequence analysis tandem mass spectrometry tumor cell line X ray crystallography Animals Cell Communication Cell Line, Tumor Cell Movement Coculture Techniques Crystallography, X-Ray Culture Media, Conditioned Cytoskeleton Gene Expression Regulation, Neoplastic Gene Regulatory Networks Heme Oxygenase-1 Humans Male Mice Oligonucleotide Array Sequence Analysis Prostatic Neoplasms Protein Binding Proteomics Pseudopodia Sequence Analysis, RNA Tandem Mass Spectrometry Transcriptome |
| spellingShingle |
conditioned medium heme oxygenase 1 protein binding transcriptome animal cell communication cell motion coculture conditioned medium cytoskeleton DNA microarray drug effects enzymology gene expression regulation gene regulatory network genetics human male metabolism mouse pathology pharmacology prostate tumor proteomics pseudopodium sequence analysis tandem mass spectrometry tumor cell line X ray crystallography Animals Cell Communication Cell Line, Tumor Cell Movement Coculture Techniques Crystallography, X-Ray Culture Media, Conditioned Cytoskeleton Gene Expression Regulation, Neoplastic Gene Regulatory Networks Heme Oxygenase-1 Humans Male Mice Oligonucleotide Array Sequence Analysis Prostatic Neoplasms Protein Binding Proteomics Pseudopodia Sequence Analysis, RNA Tandem Mass Spectrometry Transcriptome Heme oxygenase-1 in the forefront of a multi-molecular network that governs cell-cell contacts and filopodia-induced zippering in prostate cancer |
| topic_facet |
conditioned medium heme oxygenase 1 protein binding transcriptome animal cell communication cell motion coculture conditioned medium cytoskeleton DNA microarray drug effects enzymology gene expression regulation gene regulatory network genetics human male metabolism mouse pathology pharmacology prostate tumor proteomics pseudopodium sequence analysis tandem mass spectrometry tumor cell line X ray crystallography Animals Cell Communication Cell Line, Tumor Cell Movement Coculture Techniques Crystallography, X-Ray Culture Media, Conditioned Cytoskeleton Gene Expression Regulation, Neoplastic Gene Regulatory Networks Heme Oxygenase-1 Humans Male Mice Oligonucleotide Array Sequence Analysis Prostatic Neoplasms Protein Binding Proteomics Pseudopodia Sequence Analysis, RNA Tandem Mass Spectrometry Transcriptome |
| description |
Prostate cancer (PCa) cells display abnormal expression of cytoskeletal proteins resulting in an augmented capacity to resist chemotherapy and colonize distant organs. We have previously shown that heme oxygenase 1 (HO-1) is implicated in cell morphology regulation in PCa. Here, through a multi 'omics' approach we define the HO-1 interactome in PCa, identifying HO-1 molecular partners associated with the integrity of the cellular cytoskeleton. The bioinformatics screening for these cytoskeletal-related partners reveal that they are highly misregulated in prostate adenocarcinoma compared with normal prostate tissue. Under HO-1 induction, PCa cells present reduced frequency in migration events, trajectory and cell velocity and, a significant higher proportion of filopodia-like protrusions favoring zippering among neighboring cells. Moreover forced expression of HO-1 was also capable of altering cell protrusions in transwell co-culture systems of PCa cells with MC3T3 cells (pre-osteoblastic cell line). Accordingly, these effects were reversed under siHO. Transcriptomics profiling evidenced significant modulation of key markers related to cell adhesion and cell-cell communication under HO-1 induction. The integration from our omics-based research provides a four molecular pathway foundation (ANXA2/HMGA1/POU3F1; NFRSF13/GSN; TMOD3/RAI14/VWF; and PLAT/PLAU) behind HO-1 regulation of tumor cytoskeletal cell compartments. The complementary proteomics and transcriptomics approaches presented here promise to move us closer to unravel the molecular framework underpinning HO-1 involvement in the modulation of cytoskeleton pathways, pushing toward a less aggressive phenotype in PCa. |
| title |
Heme oxygenase-1 in the forefront of a multi-molecular network that governs cell-cell contacts and filopodia-induced zippering in prostate cancer |
| title_short |
Heme oxygenase-1 in the forefront of a multi-molecular network that governs cell-cell contacts and filopodia-induced zippering in prostate cancer |
| title_full |
Heme oxygenase-1 in the forefront of a multi-molecular network that governs cell-cell contacts and filopodia-induced zippering in prostate cancer |
| title_fullStr |
Heme oxygenase-1 in the forefront of a multi-molecular network that governs cell-cell contacts and filopodia-induced zippering in prostate cancer |
| title_full_unstemmed |
Heme oxygenase-1 in the forefront of a multi-molecular network that governs cell-cell contacts and filopodia-induced zippering in prostate cancer |
| title_sort |
heme oxygenase-1 in the forefront of a multi-molecular network that governs cell-cell contacts and filopodia-induced zippering in prostate cancer |
| publishDate |
2016 |
| url |
https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_20414889_v7_n12_pe2570_Paez http://hdl.handle.net/20.500.12110/paper_20414889_v7_n12_pe2570_Paez |
| _version_ |
1768541915187249152 |