i3S-Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Rua Alfredo Allen, 208, 4200-135 Porto, Portugal.
IPATIMUP-Instituto de Patologia e Imunologia Molecular da Universidade do Porto, Rua Dr. Roberto Frias s/n, 4200-465 Porto, Portugal.
Int J Mol Sci. 2022 Aug 3;23(15):8622. doi: 10.3390/ijms23158622.
Animal cells display great diversity in their shape. These morphological characteristics result from crosstalk between the plasma membrane and the force-generating capacities of the cytoskeleton macromolecules. Changes in cell shape are not merely byproducts of cell fate determinants, they also actively drive cell fate decisions, including proliferation and differentiation. Global and local changes in cell shape alter the transcriptional program by a multitude of mechanisms, including the regulation of physical links between the plasma membrane and the nuclear envelope and the mechanical modulation of cation channels and signalling molecules. It is therefore not surprising that anomalies in cell shape contribute to several diseases, including cancer. In this review, we discuss the possibility that the constraints imposed by cell shape determine the behaviour of normal and pro-tumour cells by organizing the whole interconnected regulatory network. In turn, cell behaviour might stabilize cells into discrete shapes. However, to progress towards a fully transformed phenotype and to acquire plasticity properties, pro-tumour cells might need to escape these cell shape restrictions. Thus, robust controls of the cell shape machinery may represent a critical safeguard against carcinogenesis.
动物细胞在形状上表现出极大的多样性。这些形态特征源于质膜与细胞骨架大分子产生力的能力之间的相互作用。细胞形状的变化不仅仅是细胞命运决定因素的副产品，它们还积极地驱动细胞命运决定，包括增殖和分化。细胞形状的全局和局部变化通过多种机制改变转录程序，包括调节质膜和核膜之间的物理连接以及机械调节阳离子通道和信号分子。因此，细胞形状的异常会导致多种疾病，包括癌症，这并不奇怪。在这篇综述中，我们讨论了这样一种可能性，即细胞形状施加的限制通过组织整个相互关联的调控网络来决定正常和肿瘤前细胞的行为。反过来，细胞行为可能会将细胞稳定为离散的形状。然而，为了向完全转化的表型发展并获得可塑性特性，肿瘤前细胞可能需要逃避这些细胞形状的限制。因此，对细胞形状机制的稳健控制可能是防止癌变的关键保障。
