Cancer Cell Acid Adaptation Gene Expression Response is Correlated to Tumor-Specific Tissue Expression Profiles and Patient Survival
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Cancer Cell Acid Adaptation Gene Expression Response is Correlated to Tumor-Specific Tissue Expression Profiles and Patient Survival. / Yao, Jiayi; Czaplinska, Dominika; Ialchina, Renata; Schnipper, Julie; Liu, Bin; Sandelin, Albin; Pedersen, Stine Falsig.
I: Cancers, Bind 12, Nr. 8, 2183, 2020.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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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 -
ID: 249769113