Mitochondrial Function Differences between Tumor Tissue of Human Metastatic and Premetastatic CRC
Most colorectal cancer (CRC) patients die as a consequence of metastasis. Mitochondrial dysfunction could enhance cancer development and metastatic progression. We aimed to evaluate the adaptations associated with mitochondrial function in tumor tissues from stages III and IV of human CRC and whethe...
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MDPI AG
2022-02-01
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| Online Access: | https://www.mdpi.com/2079-7737/11/2/293 |
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| author | Reyniel Hernández-López Margalida Torrens-Mas Daniel G. Pons Maria M. Company Esther Falcó Teresa Fernández Javier M. Ibarra de la Rosa Pilar Roca Jordi Oliver Jorge Sastre-Serra |
| author_facet | Reyniel Hernández-López Margalida Torrens-Mas Daniel G. Pons Maria M. Company Esther Falcó Teresa Fernández Javier M. Ibarra de la Rosa Pilar Roca Jordi Oliver Jorge Sastre-Serra |
| author_sort | Reyniel Hernández-López |
| collection | DOAJ |
| description | Most colorectal cancer (CRC) patients die as a consequence of metastasis. Mitochondrial dysfunction could enhance cancer development and metastatic progression. We aimed to evaluate the adaptations associated with mitochondrial function in tumor tissues from stages III and IV of human CRC and whether they could ultimately be used as a therapeutic target in metastatic colorectal cancer (mCRC). We analyzed the protein levels by Western blotting and the enzymatic activities of proteins involved in mitochondrial function, as well as the amount of mitochondrial DNA (mtDNA), by real-time PCR, analyzing samples of non-tumor adjacent tissue and tumor tissue from stages III and IV CRC patients without radio- or chemotherapy treatment prior to surgery. Our data indicate that the tumor tissue of pre-metastatic stage III CRC exhibited an oxidant metabolic profile very similar to the samples of non-tumor adjacent tissue of both stages. Notable differences in the protein expression levels of ATPase, IDH2, LDHA, and SIRT1, as well as mtDNA amount, were detected between the samples of non-tumor adjacent tissue and tumor tissue from metastatic CRC patients. These findings suggest a shift in the oxidative metabolic profile that takes place in the tumor tissue once the metastatic stage has been reached. Tumor tissue oxidative metabolism contributes to promote and maintain the metastatic phenotype, with evidence of mitochondrial function impairment in stage IV tumor tissue. |
| first_indexed | 2024-03-09T22:35:02Z |
| format | Article |
| id | doaj.art-acf11de8e2f944ad9d4ba20aa48eded8 |
| institution | Directory Open Access Journal |
| issn | 2079-7737 |
| language | English |
| last_indexed | 2024-03-09T22:35:02Z |
| publishDate | 2022-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biology |
| spelling | doaj.art-acf11de8e2f944ad9d4ba20aa48eded82023-11-23T18:50:59ZengMDPI AGBiology2079-77372022-02-0111229310.3390/biology11020293Mitochondrial Function Differences between Tumor Tissue of Human Metastatic and Premetastatic CRCReyniel Hernández-López0Margalida Torrens-Mas1Daniel G. Pons2Maria M. Company3Esther Falcó4Teresa Fernández5Javier M. Ibarra de la Rosa6Pilar Roca7Jordi Oliver8Jorge Sastre-Serra9Grupo Multidisciplinar de Oncología Traslacional, Institut Universitari d´Investigació en Ciències de la Salut (IUNICS), Universitat de les Illes Balears, E-07122 Palma de Mallorca, Illes Balears, SpainGrupo Multidisciplinar de Oncología Traslacional, Institut Universitari d´Investigació en Ciències de la Salut (IUNICS), Universitat de les Illes Balears, E-07122 Palma de Mallorca, Illes Balears, SpainGrupo Multidisciplinar de Oncología Traslacional, Institut Universitari d´Investigació en Ciències de la Salut (IUNICS), Universitat de les Illes Balears, E-07122 Palma de Mallorca, Illes Balears, SpainInstituto de Investigación Sanitaria de las Islas Baleares (IdISBa), Hospital Universitario Son Espases, Edificio S, E-07120 Palma de Mallorca, Illes Balears, SpainInstituto de Investigación Sanitaria de las Islas Baleares (IdISBa), Hospital Universitario Son Espases, Edificio S, E-07120 Palma de Mallorca, Illes Balears, SpainInstituto de Investigación Sanitaria de las Islas Baleares (IdISBa), Hospital Universitario Son Espases, Edificio S, E-07120 Palma de Mallorca, Illes Balears, SpainInstituto de Investigación Sanitaria de las Islas Baleares (IdISBa), Hospital Universitario Son Espases, Edificio S, E-07120 Palma de Mallorca, Illes Balears, SpainGrupo Multidisciplinar de Oncología Traslacional, Institut Universitari d´Investigació en Ciències de la Salut (IUNICS), Universitat de les Illes Balears, E-07122 Palma de Mallorca, Illes Balears, SpainGrupo Multidisciplinar de Oncología Traslacional, Institut Universitari d´Investigació en Ciències de la Salut (IUNICS), Universitat de les Illes Balears, E-07122 Palma de Mallorca, Illes Balears, SpainGrupo Multidisciplinar de Oncología Traslacional, Institut Universitari d´Investigació en Ciències de la Salut (IUNICS), Universitat de les Illes Balears, E-07122 Palma de Mallorca, Illes Balears, SpainMost colorectal cancer (CRC) patients die as a consequence of metastasis. Mitochondrial dysfunction could enhance cancer development and metastatic progression. We aimed to evaluate the adaptations associated with mitochondrial function in tumor tissues from stages III and IV of human CRC and whether they could ultimately be used as a therapeutic target in metastatic colorectal cancer (mCRC). We analyzed the protein levels by Western blotting and the enzymatic activities of proteins involved in mitochondrial function, as well as the amount of mitochondrial DNA (mtDNA), by real-time PCR, analyzing samples of non-tumor adjacent tissue and tumor tissue from stages III and IV CRC patients without radio- or chemotherapy treatment prior to surgery. Our data indicate that the tumor tissue of pre-metastatic stage III CRC exhibited an oxidant metabolic profile very similar to the samples of non-tumor adjacent tissue of both stages. Notable differences in the protein expression levels of ATPase, IDH2, LDHA, and SIRT1, as well as mtDNA amount, were detected between the samples of non-tumor adjacent tissue and tumor tissue from metastatic CRC patients. These findings suggest a shift in the oxidative metabolic profile that takes place in the tumor tissue once the metastatic stage has been reached. Tumor tissue oxidative metabolism contributes to promote and maintain the metastatic phenotype, with evidence of mitochondrial function impairment in stage IV tumor tissue.https://www.mdpi.com/2079-7737/11/2/293colorectal cancermetastatic cancermitochondrial functionOXPHOSmtDNA |
| spellingShingle | Reyniel Hernández-López Margalida Torrens-Mas Daniel G. Pons Maria M. Company Esther Falcó Teresa Fernández Javier M. Ibarra de la Rosa Pilar Roca Jordi Oliver Jorge Sastre-Serra Mitochondrial Function Differences between Tumor Tissue of Human Metastatic and Premetastatic CRC Biology colorectal cancer metastatic cancer mitochondrial function OXPHOS mtDNA |
| title | Mitochondrial Function Differences between Tumor Tissue of Human Metastatic and Premetastatic CRC |
| title_full | Mitochondrial Function Differences between Tumor Tissue of Human Metastatic and Premetastatic CRC |
| title_fullStr | Mitochondrial Function Differences between Tumor Tissue of Human Metastatic and Premetastatic CRC |
| title_full_unstemmed | Mitochondrial Function Differences between Tumor Tissue of Human Metastatic and Premetastatic CRC |
| title_short | Mitochondrial Function Differences between Tumor Tissue of Human Metastatic and Premetastatic CRC |
| title_sort | mitochondrial function differences between tumor tissue of human metastatic and premetastatic crc |
| topic | colorectal cancer metastatic cancer mitochondrial function OXPHOS mtDNA |
| url | https://www.mdpi.com/2079-7737/11/2/293 |
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