ABCA1 transporter promotes the motility of human melanoma cells by modulating their plasma membrane organization
Abstract Background Melanoma is one of the most aggressive and deadliest skin tumor. Cholesterol content in melanoma cells is elevated, and a portion of it accumulates into lipid rafts. Therefore, the plasma membrane cholesterol and its lateral organization might be directly linked with tumor develo...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2023-06-01
|
| Series: | Biological Research |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s40659-023-00443-4 |
| _version_ | 1827923161373474816 |
|---|---|
| author | Ambroise Wu Ewa Mazurkiewicz Piotr Donizy Krzysztof Kotowski Małgorzata Pieniazek Antonina J. Mazur Aleksander Czogalla Tomasz Trombik |
| author_facet | Ambroise Wu Ewa Mazurkiewicz Piotr Donizy Krzysztof Kotowski Małgorzata Pieniazek Antonina J. Mazur Aleksander Czogalla Tomasz Trombik |
| author_sort | Ambroise Wu |
| collection | DOAJ |
| description | Abstract Background Melanoma is one of the most aggressive and deadliest skin tumor. Cholesterol content in melanoma cells is elevated, and a portion of it accumulates into lipid rafts. Therefore, the plasma membrane cholesterol and its lateral organization might be directly linked with tumor development. ATP Binding Cassette A1 (ABCA1) transporter modulates physico-chemical properties of the plasma membrane by modifying cholesterol distribution. Several studies linked the activity of the transporter with a different outcome of tumor progression depending on which type. However, no direct link between human melanoma progression and ABCA1 activity has been reported yet. Methods An immunohistochemical study on the ABCA1 level in 110 patients-derived melanoma tumors was performed to investigate the potential association of the transporter with melanoma stage of progression and prognosis. Furthermore, proliferation, migration and invasion assays, extracellular-matrix degradation assay, immunochemistry on proteins involved in migration processes and a combination of biophysical microscopy analysis of the plasma membrane organization of Hs294T human melanoma wild type, control (scrambled), ABCA1 Knockout (ABCA1 KO) and ABCA1 chemically inactivated cells were used to study the impact of ABCA1 activity on human melanoma metastasis processes. Results The immunohistochemical analysis of clinical samples showed that high level of ABCA1 transporter in human melanoma is associated with a poor prognosis. Depletion or inhibition of ABCA1 impacts invasion capacities of aggressive melanoma cells. Loss of ABCA1 activity partially prevented cellular motility by affecting active focal adhesions formation via blocking clustering of phosphorylated focal adhesion kinases and active integrin β3. Moreover, ABCA1 activity regulated the lateral organization of the plasma membrane in melanoma cells. Disrupting this organization, by increasing the content of cholesterol, also blocked active focal adhesion formation. Conclusion Human melanoma cells reorganize their plasma membrane cholesterol content and organization via ABCA1 activity to promote motility processes and aggressiveness potential. Therefore, ABCA1 may contribute to tumor progression and poor prognosis, suggesting ABCA1 to be a potential metastatic marker in melanoma. |
| first_indexed | 2024-03-13T04:52:57Z |
| format | Article |
| id | doaj.art-a0c50c2d9f1347c9b8dcb34392164053 |
| institution | Directory Open Access Journal |
| issn | 0717-6287 |
| language | English |
| last_indexed | 2024-03-13T04:52:57Z |
| publishDate | 2023-06-01 |
| publisher | BMC |
| record_format | Article |
| series | Biological Research |
| spelling | doaj.art-a0c50c2d9f1347c9b8dcb343921640532023-06-18T11:07:02ZengBMCBiological Research0717-62872023-06-0156112110.1186/s40659-023-00443-4ABCA1 transporter promotes the motility of human melanoma cells by modulating their plasma membrane organizationAmbroise Wu0Ewa Mazurkiewicz1Piotr Donizy2Krzysztof Kotowski3Małgorzata Pieniazek4Antonina J. Mazur5Aleksander Czogalla6Tomasz Trombik7Department of Cytobiochemistry, Faculty of Biotechnology, University of WrocławDepartment of Cell Pathology, Faculty of Biotechnology, University of WrocławDepartment of Clinical and Experimental Pathology, Wrocław Medical UniversityDepartment of Clinical and Experimental Pathology, Wrocław Medical UniversityDepartment of Oncology and Division of Surgical Oncology, Wrocław Medical UniversityDepartment of Cell Pathology, Faculty of Biotechnology, University of WrocławDepartment of Cytobiochemistry, Faculty of Biotechnology, University of WrocławDepartment of Biophysics, Faculty of Biotechnology, University of WrocławAbstract Background Melanoma is one of the most aggressive and deadliest skin tumor. Cholesterol content in melanoma cells is elevated, and a portion of it accumulates into lipid rafts. Therefore, the plasma membrane cholesterol and its lateral organization might be directly linked with tumor development. ATP Binding Cassette A1 (ABCA1) transporter modulates physico-chemical properties of the plasma membrane by modifying cholesterol distribution. Several studies linked the activity of the transporter with a different outcome of tumor progression depending on which type. However, no direct link between human melanoma progression and ABCA1 activity has been reported yet. Methods An immunohistochemical study on the ABCA1 level in 110 patients-derived melanoma tumors was performed to investigate the potential association of the transporter with melanoma stage of progression and prognosis. Furthermore, proliferation, migration and invasion assays, extracellular-matrix degradation assay, immunochemistry on proteins involved in migration processes and a combination of biophysical microscopy analysis of the plasma membrane organization of Hs294T human melanoma wild type, control (scrambled), ABCA1 Knockout (ABCA1 KO) and ABCA1 chemically inactivated cells were used to study the impact of ABCA1 activity on human melanoma metastasis processes. Results The immunohistochemical analysis of clinical samples showed that high level of ABCA1 transporter in human melanoma is associated with a poor prognosis. Depletion or inhibition of ABCA1 impacts invasion capacities of aggressive melanoma cells. Loss of ABCA1 activity partially prevented cellular motility by affecting active focal adhesions formation via blocking clustering of phosphorylated focal adhesion kinases and active integrin β3. Moreover, ABCA1 activity regulated the lateral organization of the plasma membrane in melanoma cells. Disrupting this organization, by increasing the content of cholesterol, also blocked active focal adhesion formation. Conclusion Human melanoma cells reorganize their plasma membrane cholesterol content and organization via ABCA1 activity to promote motility processes and aggressiveness potential. Therefore, ABCA1 may contribute to tumor progression and poor prognosis, suggesting ABCA1 to be a potential metastatic marker in melanoma.https://doi.org/10.1186/s40659-023-00443-4ABCA1Cell motilityCholesterolHuman melanomaPlasma membrane |
| spellingShingle | Ambroise Wu Ewa Mazurkiewicz Piotr Donizy Krzysztof Kotowski Małgorzata Pieniazek Antonina J. Mazur Aleksander Czogalla Tomasz Trombik ABCA1 transporter promotes the motility of human melanoma cells by modulating their plasma membrane organization Biological Research ABCA1 Cell motility Cholesterol Human melanoma Plasma membrane |
| title | ABCA1 transporter promotes the motility of human melanoma cells by modulating their plasma membrane organization |
| title_full | ABCA1 transporter promotes the motility of human melanoma cells by modulating their plasma membrane organization |
| title_fullStr | ABCA1 transporter promotes the motility of human melanoma cells by modulating their plasma membrane organization |
| title_full_unstemmed | ABCA1 transporter promotes the motility of human melanoma cells by modulating their plasma membrane organization |
| title_short | ABCA1 transporter promotes the motility of human melanoma cells by modulating their plasma membrane organization |
| title_sort | abca1 transporter promotes the motility of human melanoma cells by modulating their plasma membrane organization |
| topic | ABCA1 Cell motility Cholesterol Human melanoma Plasma membrane |
| url | https://doi.org/10.1186/s40659-023-00443-4 |
| work_keys_str_mv | AT ambroisewu abca1transporterpromotesthemotilityofhumanmelanomacellsbymodulatingtheirplasmamembraneorganization AT ewamazurkiewicz abca1transporterpromotesthemotilityofhumanmelanomacellsbymodulatingtheirplasmamembraneorganization AT piotrdonizy abca1transporterpromotesthemotilityofhumanmelanomacellsbymodulatingtheirplasmamembraneorganization AT krzysztofkotowski abca1transporterpromotesthemotilityofhumanmelanomacellsbymodulatingtheirplasmamembraneorganization AT małgorzatapieniazek abca1transporterpromotesthemotilityofhumanmelanomacellsbymodulatingtheirplasmamembraneorganization AT antoninajmazur abca1transporterpromotesthemotilityofhumanmelanomacellsbymodulatingtheirplasmamembraneorganization AT aleksanderczogalla abca1transporterpromotesthemotilityofhumanmelanomacellsbymodulatingtheirplasmamembraneorganization AT tomasztrombik abca1transporterpromotesthemotilityofhumanmelanomacellsbymodulatingtheirplasmamembraneorganization |