TY - JOUR

T1 - Cancer stem cells

T2 - Emergent nature of tumor emergency

AU - Efremov, Yaroslav R.

AU - Proskurina, Anastasia S.

AU - Potter, Ekaterina A.

AU - Dolgova, Evgenia V.

AU - Efremova, Oksana V.

AU - Taranov, Oleg S.

AU - Ostanin, Aleksandr A.

AU - Chernykh, Elena R.

AU - Kolchanov, Nikolay A.

AU - Bogachev, Sergey S.

N1 - Funding Information: This study was supported by the State scientific project N 0324-2018-0019 and by the Integration project of the Siberian Branch of the Russian Academy of Sciences Reconstruction, computer analysis and modeling of the structural and functional organization of biomedical-significant gene networks (project N 0324-2018-0021). Publisher Copyright: © 2018 Efremov, Proskurina, Potter, Dolgova, Efremova, Taranov, Ostanin, Chernykh, Kolchanov and Bogachev. Copyright: Copyright 2020 Elsevier B.V., All rights reserved.

PY - 2018/11/16

Y1 - 2018/11/16

N2 - A functional analysis of 167 genes overexpressed in Krebs-2 tumor initiating cells was performed. In the first part of the study, the genes were analyzed for their belonging to one or more of the three groups, which represent the three major phenotypic manifestation of malignancy of cancer cells, namely (1) proliferative self-sufficiency, (2) invasive growth and metastasis, and (3) multiple drug resistance. 96 genes out of 167 were identified as possible contributors to at least one of these fundamental properties. It was also found that substantial part of these genes are also known as genes responsible for formation and/or maintenance of the stemness of normal pluri-/multipotent stem cells. These results suggest that the malignancy is simply the ability to maintain the stem cell specific genes expression profile, and, as a consequence, the stemness itself regardless of the controlling effect of stem niches. In the second part of the study, three stress factors combined into the single concept of “generalized cellular stress,” which are assumed to activate the expression of these genes, were defined. In addition, possible mechanisms for such activation were identified. The data obtained suggest the existence of a mechanism for the de novo formation of a pluripotent/stem phenotype in the subpopulation of “committed” tumor cells.

AB - A functional analysis of 167 genes overexpressed in Krebs-2 tumor initiating cells was performed. In the first part of the study, the genes were analyzed for their belonging to one or more of the three groups, which represent the three major phenotypic manifestation of malignancy of cancer cells, namely (1) proliferative self-sufficiency, (2) invasive growth and metastasis, and (3) multiple drug resistance. 96 genes out of 167 were identified as possible contributors to at least one of these fundamental properties. It was also found that substantial part of these genes are also known as genes responsible for formation and/or maintenance of the stemness of normal pluri-/multipotent stem cells. These results suggest that the malignancy is simply the ability to maintain the stem cell specific genes expression profile, and, as a consequence, the stemness itself regardless of the controlling effect of stem niches. In the second part of the study, three stress factors combined into the single concept of “generalized cellular stress,” which are assumed to activate the expression of these genes, were defined. In addition, possible mechanisms for such activation were identified. The data obtained suggest the existence of a mechanism for the de novo formation of a pluripotent/stem phenotype in the subpopulation of “committed” tumor cells.

KW - Cancer stem cell

KW - Carcinogenesis

KW - Genes-markers of stemness

KW - Hypoxia

KW - Induction of pluripotency

KW - Oxidative stress

KW - TAMRA+ cells

KW - Xenobiotics

UR - http://www.scopus.com/inward/record.url?scp=85067560810&partnerID=8YFLogxK

U2 - 10.3389/fgene.2018.00544

DO - 10.3389/fgene.2018.00544

M3 - Article

C2 - 30505319

AN - SCOPUS:85067560810

VL - 9

JO - Frontiers in Genetics

JF - Frontiers in Genetics

SN - 1664-8021

M1 - 544

ER -