Mondal Samuel, Becskei Attila
Biozentrum, University of Basel, Spitalstrasse 41, Basel 4056, Switzerland.
Comput Struct Biotechnol J. 2024 Jun 10;23:2534-2547. doi: 10.1016/j.csbj.2024.06.004. eCollection 2024 Dec.
Cancers share common cellular and physiological features. Little is known about whether distinctive gene expression patterns can be displayed at the single-cell level by gene families in cancer cells. The expression of gene homologs within a family can exhibit concurrence and exclusivity. Concurrence can promote all-or-none expression patterns of related genes and underlie alternative physiological states. Conversely, exclusive gene families express the same or similar number of homologs in each cell, allowing a broad repertoire of cell identities to be generated. We show that gene families involved in the cell-cycle and antigen presentation are expressed concurrently. Concurrence in the DNA replication complex MCM reflects the replicative status of cells, including cell lines and cancer-derived organoids. Exclusive expression requires precise regulatory mechanism, but cancer cells retain this form of control for ion homeostasis and extend it to gene families involved in cell migration. Thus, the cell adhesion-based identity of healthy cells is transformed to an identity based on migration in the population of cancer cells, reminiscent of epithelial-mesenchymal transition.
癌症具有共同的细胞和生理特征。关于癌细胞中的基因家族是否能在单细胞水平上表现出独特的基因表达模式，人们所知甚少。一个家族内基因同源物的表达可以表现出同时性和排他性。同时性可以促进相关基因的全或无表达模式，并构成替代生理状态的基础。相反，排他性基因家族在每个细胞中表达相同或相似数量的同源物，从而产生广泛的细胞身份。我们发现，参与细胞周期和抗原呈递的基因家族是同时表达的。DNA复制复合体MCM中的同时性反映了细胞的复制状态，包括细胞系和癌症衍生的类器官。排他性表达需要精确的调控机制，但癌细胞保留了这种对离子稳态的控制形式，并将其扩展到参与细胞迁移的基因家族。因此，健康细胞基于细胞粘附的身份在癌细胞群体中转变为基于迁移的身份，这让人联想到上皮-间质转化。
