Inhibition of Tunneling Nanotubes between Cancer Cell and the Endothelium Alters the Metastatic Phenotype
The interaction of tumor cells with blood vessels is one of the key steps during cancer metastasis. Metastatic cancer cells exhibit phenotypic state changes during this interaction: (1) they form tunneling nanotubes (TNTs) with endothelial cells, which act as a conduit for intercellular communicatio...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-06-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/11/6161 |
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| author | Chinmayee Dash Tanmoy Saha Shiladitya Sengupta Hae Lin Jang |
| author_facet | Chinmayee Dash Tanmoy Saha Shiladitya Sengupta Hae Lin Jang |
| author_sort | Chinmayee Dash |
| collection | DOAJ |
| description | The interaction of tumor cells with blood vessels is one of the key steps during cancer metastasis. Metastatic cancer cells exhibit phenotypic state changes during this interaction: (1) they form tunneling nanotubes (TNTs) with endothelial cells, which act as a conduit for intercellular communication; and (2) metastatic cancer cells change in order to acquire an elongated phenotype, instead of the classical cellular aggregates or mammosphere-like structures, which it forms in three-dimensional cultures. Here, we demonstrate mechanistically that a siRNA-based knockdown of the exocyst complex protein Sec3 inhibits TNT formation. Furthermore, a set of pharmacological inhibitors for Rho GTPase–exocyst complex-mediated cytoskeletal remodeling is introduced, which inhibits TNT formation, and induces the reversal of the more invasive phenotype of cancer cell (spindle-like) into a less invasive phenotype (cellular aggregates or mammosphere). Our results offer mechanistic insights into this nanoscale communication and shift of phenotypic state during cancer–endothelial interactions. |
| first_indexed | 2024-03-10T10:38:37Z |
| format | Article |
| id | doaj.art-fe5adecd33fd4a078bf822d7c7e79987 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T10:38:37Z |
| publishDate | 2021-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-fe5adecd33fd4a078bf822d7c7e799872023-11-21T23:10:30ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-06-012211616110.3390/ijms22116161Inhibition of Tunneling Nanotubes between Cancer Cell and the Endothelium Alters the Metastatic PhenotypeChinmayee Dash0Tanmoy Saha1Shiladitya Sengupta2Hae Lin Jang3Center for Engineered Therapeutics, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02139, USACenter for Engineered Therapeutics, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02139, USACenter for Engineered Therapeutics, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02139, USACenter for Engineered Therapeutics, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02139, USAThe interaction of tumor cells with blood vessels is one of the key steps during cancer metastasis. Metastatic cancer cells exhibit phenotypic state changes during this interaction: (1) they form tunneling nanotubes (TNTs) with endothelial cells, which act as a conduit for intercellular communication; and (2) metastatic cancer cells change in order to acquire an elongated phenotype, instead of the classical cellular aggregates or mammosphere-like structures, which it forms in three-dimensional cultures. Here, we demonstrate mechanistically that a siRNA-based knockdown of the exocyst complex protein Sec3 inhibits TNT formation. Furthermore, a set of pharmacological inhibitors for Rho GTPase–exocyst complex-mediated cytoskeletal remodeling is introduced, which inhibits TNT formation, and induces the reversal of the more invasive phenotype of cancer cell (spindle-like) into a less invasive phenotype (cellular aggregates or mammosphere). Our results offer mechanistic insights into this nanoscale communication and shift of phenotypic state during cancer–endothelial interactions.https://www.mdpi.com/1422-0067/22/11/6161tunneling nanotube (TNT)metastasisRhoGTPase inhibitorphenotypic plasticityexocyst complexactin remodeling |
| spellingShingle | Chinmayee Dash Tanmoy Saha Shiladitya Sengupta Hae Lin Jang Inhibition of Tunneling Nanotubes between Cancer Cell and the Endothelium Alters the Metastatic Phenotype International Journal of Molecular Sciences tunneling nanotube (TNT) metastasis RhoGTPase inhibitor phenotypic plasticity exocyst complex actin remodeling |
| title | Inhibition of Tunneling Nanotubes between Cancer Cell and the Endothelium Alters the Metastatic Phenotype |
| title_full | Inhibition of Tunneling Nanotubes between Cancer Cell and the Endothelium Alters the Metastatic Phenotype |
| title_fullStr | Inhibition of Tunneling Nanotubes between Cancer Cell and the Endothelium Alters the Metastatic Phenotype |
| title_full_unstemmed | Inhibition of Tunneling Nanotubes between Cancer Cell and the Endothelium Alters the Metastatic Phenotype |
| title_short | Inhibition of Tunneling Nanotubes between Cancer Cell and the Endothelium Alters the Metastatic Phenotype |
| title_sort | inhibition of tunneling nanotubes between cancer cell and the endothelium alters the metastatic phenotype |
| topic | tunneling nanotube (TNT) metastasis RhoGTPase inhibitor phenotypic plasticity exocyst complex actin remodeling |
| url | https://www.mdpi.com/1422-0067/22/11/6161 |
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