Bukkuri Anuraag, Adler Frederick R
Department of Computational and Systems Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA, United States.
School of Biological Sciences, University of Utah, Salt Lake City, UT, United States; Department of Mathematics, University of Utah, Salt Lake City, UT, United States; Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, United States.
Cells Dev. 2024 Dec;180:203964. doi: 10.1016/j.cdev.2024.203964. Epub 2024 Aug 14.
The current dogma in cancer biology contends that cancer is an identity problem: mutations in a cell's DNA cause it to "go rogue" and proliferate out of control. However, this largely ignores the role of cell-cell interaction and fails to explain phenomena such as cancer reversion, the existence of cancers without mutations, and foreign-body carcinogenesis. In this proof-of-concept paper, we draw on criminology to propose that cancer may alternatively be conceptualized as a relational problem: Although a cell's genetics is essential, the influence of its interaction with other cells is equally important in determining its phenotype. We create a simple agent-based network model of interactions among normal and cancer cells to demonstrate this idea. We find that both high mutation rates and low levels of connectivity among cells can promote oncogenesis. Viewing cancer as a breakdown in communication networks among cells in a tissue complements the gene-centric paradigm nicely and provides a novel perspective for understanding and treating cancer.
癌症生物学的当前教条认为,癌症是一个身份问题:细胞DNA中的突变使其“失控”并失控增殖。然而,这在很大程度上忽略了细胞间相互作用的作用,并且无法解释诸如癌症逆转、无突变癌症的存在以及异物致癌等现象。在这篇概念验证论文中,我们借鉴犯罪学提出,癌症也可以被概念化为一个关系问题:虽然细胞的遗传学至关重要,但它与其他细胞相互作用的影响在决定其表型方面同样重要。我们创建了一个基于简单主体的正常细胞和癌细胞相互作用网络模型来证明这一观点。我们发现,高突变率和细胞间低连接水平都可以促进肿瘤发生。将癌症视为组织中细胞间通信网络的故障,很好地补充了以基因为中心的范式,并为理解和治疗癌症提供了一个新的视角。