Intratumoral Heterogeneity Promotes Collective Cancer Invasion through NOTCH1 Variation

Cellular and molecular heterogeneity within tumors has long been associated with the progression of cancer to an aggressive phenotype and a poor prognosis. However, how such intratumoral heterogeneity contributes to the invasiveness of cancer is largely unknown. Here, using a tumor bioengineering ap...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Peter Torab, Yue Yan, Mona Ahmed, Hironobu Yamashita, Joshua I. Warrick, Jay D. Raman, David J. DeGraff, Pak Kin Wong
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	single cell analysis tumor subtypes basal luminal tumor-on-chip biosensing Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/9fd3d75d6c6547998b2dfb18ad573bc7
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:9fd3d75d6c6547998b2dfb18ad573bc7
record_format	dspace
spelling	oai:doaj.org-article:9fd3d75d6c6547998b2dfb18ad573bc72021-11-25T17:11:20ZIntratumoral Heterogeneity Promotes Collective Cancer Invasion through NOTCH1 Variation10.3390/cells101130842073-4409https://doaj.org/article/9fd3d75d6c6547998b2dfb18ad573bc72021-11-01T00:00:00Zhttps://www.mdpi.com/2073-4409/10/11/3084https://doaj.org/toc/2073-4409Cellular and molecular heterogeneity within tumors has long been associated with the progression of cancer to an aggressive phenotype and a poor prognosis. However, how such intratumoral heterogeneity contributes to the invasiveness of cancer is largely unknown. Here, using a tumor bioengineering approach, we investigate the interaction between molecular subtypes within bladder microtumors and the corresponding effects on their invasiveness. Our results reveal heterogeneous microtumors formed by multiple molecular subtypes possess enhanced invasiveness compared to individual cells, even when both cells are not invasive individually. To examine the molecular mechanism of intratumoral heterogeneity mediated invasiveness, live single cell biosensing, RNA interference, and CRISPR-Cas9 gene editing approaches were applied to investigate and control the composition of the microtumors. An agent-based computational model was also developed to evaluate the influence of NOTCH1 variation on DLL4 expression within a microtumor. The data indicate that intratumoral variation in NOTCH1 expression can lead to upregulation of DLL4 expression within the microtumor and enhancement of microtumor invasiveness. Overall, our results reveal a novel mechanism of heterogeneity mediated invasiveness through intratumoral variation of gene expression.Peter TorabYue YanMona AhmedHironobu YamashitaJoshua I. WarrickJay D. RamanDavid J. DeGraffPak Kin WongMDPI AGarticlesingle cell analysistumor subtypesbasalluminaltumor-on-chipbiosensingBiology (General)QH301-705.5ENCells, Vol 10, Iss 3084, p 3084 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	single cell analysis tumor subtypes basal luminal tumor-on-chip biosensing Biology (General) QH301-705.5
spellingShingle	single cell analysis tumor subtypes basal luminal tumor-on-chip biosensing Biology (General) QH301-705.5 Peter Torab Yue Yan Mona Ahmed Hironobu Yamashita Joshua I. Warrick Jay D. Raman David J. DeGraff Pak Kin Wong Intratumoral Heterogeneity Promotes Collective Cancer Invasion through NOTCH1 Variation
description	Cellular and molecular heterogeneity within tumors has long been associated with the progression of cancer to an aggressive phenotype and a poor prognosis. However, how such intratumoral heterogeneity contributes to the invasiveness of cancer is largely unknown. Here, using a tumor bioengineering approach, we investigate the interaction between molecular subtypes within bladder microtumors and the corresponding effects on their invasiveness. Our results reveal heterogeneous microtumors formed by multiple molecular subtypes possess enhanced invasiveness compared to individual cells, even when both cells are not invasive individually. To examine the molecular mechanism of intratumoral heterogeneity mediated invasiveness, live single cell biosensing, RNA interference, and CRISPR-Cas9 gene editing approaches were applied to investigate and control the composition of the microtumors. An agent-based computational model was also developed to evaluate the influence of NOTCH1 variation on DLL4 expression within a microtumor. The data indicate that intratumoral variation in NOTCH1 expression can lead to upregulation of DLL4 expression within the microtumor and enhancement of microtumor invasiveness. Overall, our results reveal a novel mechanism of heterogeneity mediated invasiveness through intratumoral variation of gene expression.
format	article
author	Peter Torab Yue Yan Mona Ahmed Hironobu Yamashita Joshua I. Warrick Jay D. Raman David J. DeGraff Pak Kin Wong
author_facet	Peter Torab Yue Yan Mona Ahmed Hironobu Yamashita Joshua I. Warrick Jay D. Raman David J. DeGraff Pak Kin Wong
author_sort	Peter Torab
title	Intratumoral Heterogeneity Promotes Collective Cancer Invasion through NOTCH1 Variation
title_short	Intratumoral Heterogeneity Promotes Collective Cancer Invasion through NOTCH1 Variation
title_full	Intratumoral Heterogeneity Promotes Collective Cancer Invasion through NOTCH1 Variation
title_fullStr	Intratumoral Heterogeneity Promotes Collective Cancer Invasion through NOTCH1 Variation
title_full_unstemmed	Intratumoral Heterogeneity Promotes Collective Cancer Invasion through NOTCH1 Variation
title_sort	intratumoral heterogeneity promotes collective cancer invasion through notch1 variation
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/9fd3d75d6c6547998b2dfb18ad573bc7
work_keys_str_mv	AT petertorab intratumoralheterogeneitypromotescollectivecancerinvasionthroughnotch1variation AT yueyan intratumoralheterogeneitypromotescollectivecancerinvasionthroughnotch1variation AT monaahmed intratumoralheterogeneitypromotescollectivecancerinvasionthroughnotch1variation AT hironobuyamashita intratumoralheterogeneitypromotescollectivecancerinvasionthroughnotch1variation AT joshuaiwarrick intratumoralheterogeneitypromotescollectivecancerinvasionthroughnotch1variation AT jaydraman intratumoralheterogeneitypromotescollectivecancerinvasionthroughnotch1variation AT davidjdegraff intratumoralheterogeneitypromotescollectivecancerinvasionthroughnotch1variation AT pakkinwong intratumoralheterogeneitypromotescollectivecancerinvasionthroughnotch1variation
_version_	1718412669012148224

Intratumoral Heterogeneity Promotes Collective Cancer Invasion through NOTCH1 Variation

Ejemplares similares