PTEN/FOXO3/AKT pathway regulates cell death and mediates morphogenetic differentiation of Colorectal Cancer Cells under Simulated Microgravity

Abstract Gravity is a major physical factor determining the stress and strain around cells. Both in space experiments and ground simulation, change in gravity impacts the viability and function of various types of cells as well as in vivo conditions. Cancer cells have been shown to die under microgr...

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Autores principales:	Raj Pranap Arun, Divya Sivanesan, Prasanna Vidyasekar, Rama Shanker Verma
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/9ecf14fcf5bf41daac8f7b01f633b923
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spelling	oai:doaj.org-article:9ecf14fcf5bf41daac8f7b01f633b9232021-12-02T12:32:24ZPTEN/FOXO3/AKT pathway regulates cell death and mediates morphogenetic differentiation of Colorectal Cancer Cells under Simulated Microgravity10.1038/s41598-017-06416-42045-2322https://doaj.org/article/9ecf14fcf5bf41daac8f7b01f633b9232017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-06416-4https://doaj.org/toc/2045-2322Abstract Gravity is a major physical factor determining the stress and strain around cells. Both in space experiments and ground simulation, change in gravity impacts the viability and function of various types of cells as well as in vivo conditions. Cancer cells have been shown to die under microgravity. This can be exploited for better understanding of the biology and identification of novel avenues for therapeutic intervention. Here, we described the effect of microgravity simulated using Rotational Cell Culture System-High Aspect Ratio Vessel (RCCS-HARV) on the viability and morphological changes of colorectal cancer cells. We observed DLD1, HCT116 and SW620 cells die through apoptosis under simulated microgravity (SM). Gene expression analysis on DLD1 cells showed upregulation of tumor suppressors PTEN and FOXO3; leading to AKT downregulation and further induction of apoptosis, through upregulation of CDK inhibitors CDKN2B, CDKN2D. SM induced cell clumps had elevated hypoxia and mitochondrial membrane potential that led to adaptive responses like morphogenetic changes, migration and deregulated autophagy, when shifted to normal culture conditions. This can be exploited to understand the three-dimensional (3D) biology of cancer in the aspect of stress response. This study highlights the regulation of cell function and viability under microgravity through PTEN/FOXO3/AKT pathway.Raj Pranap ArunDivya SivanesanPrasanna VidyasekarRama Shanker VermaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-15 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Raj Pranap Arun Divya Sivanesan Prasanna Vidyasekar Rama Shanker Verma PTEN/FOXO3/AKT pathway regulates cell death and mediates morphogenetic differentiation of Colorectal Cancer Cells under Simulated Microgravity
description	Abstract Gravity is a major physical factor determining the stress and strain around cells. Both in space experiments and ground simulation, change in gravity impacts the viability and function of various types of cells as well as in vivo conditions. Cancer cells have been shown to die under microgravity. This can be exploited for better understanding of the biology and identification of novel avenues for therapeutic intervention. Here, we described the effect of microgravity simulated using Rotational Cell Culture System-High Aspect Ratio Vessel (RCCS-HARV) on the viability and morphological changes of colorectal cancer cells. We observed DLD1, HCT116 and SW620 cells die through apoptosis under simulated microgravity (SM). Gene expression analysis on DLD1 cells showed upregulation of tumor suppressors PTEN and FOXO3; leading to AKT downregulation and further induction of apoptosis, through upregulation of CDK inhibitors CDKN2B, CDKN2D. SM induced cell clumps had elevated hypoxia and mitochondrial membrane potential that led to adaptive responses like morphogenetic changes, migration and deregulated autophagy, when shifted to normal culture conditions. This can be exploited to understand the three-dimensional (3D) biology of cancer in the aspect of stress response. This study highlights the regulation of cell function and viability under microgravity through PTEN/FOXO3/AKT pathway.
format	article
author	Raj Pranap Arun Divya Sivanesan Prasanna Vidyasekar Rama Shanker Verma
author_facet	Raj Pranap Arun Divya Sivanesan Prasanna Vidyasekar Rama Shanker Verma
author_sort	Raj Pranap Arun
title	PTEN/FOXO3/AKT pathway regulates cell death and mediates morphogenetic differentiation of Colorectal Cancer Cells under Simulated Microgravity
title_short	PTEN/FOXO3/AKT pathway regulates cell death and mediates morphogenetic differentiation of Colorectal Cancer Cells under Simulated Microgravity
title_full	PTEN/FOXO3/AKT pathway regulates cell death and mediates morphogenetic differentiation of Colorectal Cancer Cells under Simulated Microgravity
title_fullStr	PTEN/FOXO3/AKT pathway regulates cell death and mediates morphogenetic differentiation of Colorectal Cancer Cells under Simulated Microgravity
title_full_unstemmed	PTEN/FOXO3/AKT pathway regulates cell death and mediates morphogenetic differentiation of Colorectal Cancer Cells under Simulated Microgravity
title_sort	pten/foxo3/akt pathway regulates cell death and mediates morphogenetic differentiation of colorectal cancer cells under simulated microgravity
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/9ecf14fcf5bf41daac8f7b01f633b923
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PTEN/FOXO3/AKT pathway regulates cell death and mediates morphogenetic differentiation of Colorectal Cancer Cells under Simulated Microgravity

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