12/27/2023 0 Comments Cell polarity![]() Unlike canonical tumor suppressors that function autonomously within the cell, higher-order tissue polarity may function as a non-cell-autonomous tumor suppressor that relies on the symbiotic relationship of a community of cells to suppress the malignant phenotype of individual mutant cells in order to secure the further survival of the entire community. This Commentary concentrates on the role of cell and tissue polarity mechanisms as potential non-canonical tumor suppressors. Although loss of cell polarity was previously considered a by-product of abnormal cell accumulation, recent evidence supports the idea that disruption of cell-polarity mechanisms plays a causal role in tumor initiation. Loss of cell polarity and subsequent tissue disorganization is a hallmark of cancer ( Fig. Fortunately, cells have evolved many mechanisms to prevent such an unfavorable development. However, when this balance is skewed in favor of cell accumulation, the result is tumor development and, potentially, the death of the entire cell community. This cell community is a dynamic system that is maintained by a well-regulated balance between cell proliferation and death. ![]() The human body consists of billions of cells that exist together as an intricately organized and mutually supportive community. In this model, polarized 3D tissue organization functions as a non-canonical tumor suppressor that prevents the manifestation of neoplastic features in mutant cells and, ultimately, suppresses tumor development and progression. We suggest that polarized 3D tissue organization uses cell-cell and cell-substratum adhesion structures to reinforce and maintain the cell polarity of pre-cancerous cells. Data from in vivo and three-dimensional (3D) cell-culture models demonstrate that tissue organization attenuates the phenotypic outcome of oncogenic signaling. Furthermore, recent evidence indicates that loss of cell polarity is intimately involved in cancer: several crucial cell-polarity proteins are known proto-oncogenes or tumor suppressors, basic mechanisms of cell polarity are often targeted by oncogenic signaling pathways, and deregulation of asymmetric cell divisions of stem or progenitor cells may be responsible for abnormal self-renewal and differentiation of cancer stem cells. Disruption of cell polarity is a hallmark of cancer. ![]() Cell-polarity mechanisms are responsible not only for the diversification of cell shapes but also for regulation of the asymmetric cell divisions of stem cells that are crucial for their correct self-renewal and differentiation. ![]() Correct establishment and maintenance of cell polarity is required for the development and homeostasis of all metazoans. ![]()
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