TY - JOUR

T1 - Cancer Cell Acid Adaptation Gene Expression Response is Correlated to Tumor-Specific Tissue Expression Profiles and Patient Survival

AU - Yao, Jiayi

AU - Czaplinska, Dominika

AU - Ialchina, Renata

AU - Schnipper, Julie

AU - Liu, Bin

AU - Sandelin, Albin

AU - Pedersen, Stine Falsig

PY - 2020

Y1 - 2020

N2 - The acidic pH of the tumor microenvironment plays a critical role in driving cancer development toward a more aggressive phenotype, but the underlying mechanisms are unclear. To this end, phenotypic and genotypic changes induced by adaptation of cancer cells to chronic acidosis have been studied. However, the generality of acid adaptation patterns across cell models and their correlation to the molecular phenotypes and aggressiveness of human cancers are essentially unknown. Here, we define an acid adaptation expression response shared across three cancer cell models, dominated by metabolic rewiring, extracellular matrix remodeling, and altered cell cycle regulation and DNA damage response. We find that many genes which are upregulated by acid adaptation are significantly correlated to patient survival, and more generally, that there are clear correlations between acid adaptation expression response and gene expression change between normal and tumor tissues, for a large subset of cancer patients. Our data support the notion that tumor microenvironment acidity is one of the key factors driving the selection of aggressive cancer cells in human patient tumors, yet it also induces a growth-limiting genotype that likely limits cancer cell growth until the cells are released from acidosis, for instance during invasion.

AB - The acidic pH of the tumor microenvironment plays a critical role in driving cancer development toward a more aggressive phenotype, but the underlying mechanisms are unclear. To this end, phenotypic and genotypic changes induced by adaptation of cancer cells to chronic acidosis have been studied. However, the generality of acid adaptation patterns across cell models and their correlation to the molecular phenotypes and aggressiveness of human cancers are essentially unknown. Here, we define an acid adaptation expression response shared across three cancer cell models, dominated by metabolic rewiring, extracellular matrix remodeling, and altered cell cycle regulation and DNA damage response. We find that many genes which are upregulated by acid adaptation are significantly correlated to patient survival, and more generally, that there are clear correlations between acid adaptation expression response and gene expression change between normal and tumor tissues, for a large subset of cancer patients. Our data support the notion that tumor microenvironment acidity is one of the key factors driving the selection of aggressive cancer cells in human patient tumors, yet it also induces a growth-limiting genotype that likely limits cancer cell growth until the cells are released from acidosis, for instance during invasion.

KW - Acid adaptation

KW - Chronic acidosis

KW - Medical transcriptomics

KW - RNA sequencing

KW - Survival analysis

KW - Tumor microenvironment

U2 - 10.3390/cancers12082183

DO - 10.3390/cancers12082183

M3 - Journal article

C2 - 32764426

AN - SCOPUS:85090429834

VL - 12

JO - Cancers

JF - Cancers

SN - 2072-6694

IS - 8

M1 - 2183

ER -