Notch-Jagged signalling can give rise to clusters of cells exhibiting a hybrid epithelial/mesenchymal phenotype

Autor(es)

Boareto, Marcelo ^{[1, 2, 3]} ; Jolly, Mohit Kumar ^{[2, 4]} ; Goldman, Aaron ^{[5, 6, 7]} ; Pietila, Mika ^{[8, 9]} ; Mani, Sendurai A. ^{[8, 10]} ; Sengupta, Shiladitya ^{[5, 11, 6, 7]} ; Ben-Jacob, Eshel ^{[2, 12, 13]} ; Levine, Herbert ^{[2, 14, 4, 15]} ; Onuchic, Jose N. ^{[2, 14, 15, 16]}

Afiliação do(s) autor(es):Mostrar menos -

^[1] Univ Sao Paulo, Inst Phys, BR-05508 Sao Paulo - Brazil

^[2] Rice Univ, Ctr Theoret Biol Phys, Houston, TX 77005 - USA

^[3] Swiss Fed Inst Technol, Dept Biosyst Sci & Engn D BSSE, Mattenstr 26, CH-4058 Basel - Switzerland

^[4] Rice Univ, Dept Bioengn, Houston, TX 77005 - USA

^[5] Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 - USA

^[6] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 - USA

^[7] Brigham & Womens Hosp, Dept Med, Div Engn Med, 75 Francis St, Boston, MA 02115 - USA

^[8] Univ Texas MD Anderson Canc Ctr, Dept Translat Mol Pathol, Houston, TX 77030 - USA

^[9] Univ Turku, Turku Ctr Biotechnol, FIN-20520 Turku - Finland

^[10] Univ Texas MD Anderson Canc Ctr, Metastasis Res Ctr, Houston, TX 77025 - USA

^[11] Dana Farber Canc Inst, Boston, MA 02115 - USA

^[12] Tel Aviv Univ, Sch Phys & Astron, IL-69978 Tel Aviv - Israel

^[13] Tel Aviv Univ, Sagol Sch Neurosci, IL-69978 Tel Aviv - Israel

^[14] Rice Univ, Dept Biosci, Houston, TX 77005 - USA

^[15] Rice Univ, Dept Phys & Astron, Houston, TX 77005 - USA

^[16] Rice Univ, Dept Chem, POB 1892, Houston, TX 77005 - USA

• Tipo de documento: Artigo Científico
• Fonte: Journal of the Royal Society Interface; v. 13, n. 118 MAY 1 2016.
• Citações Web of Science: 27

Resumo

Metastasis can involve repeated cycles of epithelial-to-mesenchymal transition (EMT) and its reverse mesenchymal-to-epithelial transition. Cells can also undergo partial transitions to attain a hybrid epithelial/mesenchymal (E/M) phenotype that allows the migration of adhering cells to form a cluster of circulating tumour cells. These clusters can be apoptosis-resistant and possess an increased metastatic propensity as compared to the cells that undergo a complete EMT (mesenchymal cells). Hence, identifying the key players that can regulate the formation and maintenance of such clusters may inform anti-metastasis strategies. Here, we devise a mechanism-based theoretical model that links cell-cell communication via Notch-Delta-Jagged signalling with the regulation of EMT. We demonstrate that while both Notch-Delta and Notch-Jagged signalling can induce EMT in a population of cells, only Jagged-dominated Notch signalling, but not Delta-dominated signalling, can lead to the formation of clusters containing hybrid E/M cells. Our results offer possible mechanistic insights into the role of Jagged in tumour progression, and offer a framework to investigate the effects of other microenvironmental signals during metastasis. (AU)

• Processo FAPESP: 13/14438-8 - Estudo de redes gênicas regulatórias por meio de métodos estocásticos e de mecânica estatística
• Beneficiário: Marcelo Boareto Do Amaral
• Modalidade de apoio: Bolsas no Exterior - Estágio de Pesquisa - Doutorado Direto
• Processo FAPESP: 08/10831-9 - Tópicos em sinalização celular e bioinformática: princípios de funcionamento do circuito de sinalização Notch e aprendizagem supervisionada variacional de relevância
• Beneficiário: Marcelo Boareto Do Amaral
• Modalidade de apoio: Bolsas no Brasil - Doutorado Direto