Trends in Cell Biology
ReviewSpecial Issue: Cell CycleDivide or Conquer: Cell Cycle Regulation of Invasive Behavior
Section snippets
Linking Cell Invasion and Cell Cycle Regulation
The basement membrane (BM; see Glossary), or basal lamina, is a specialized form of extracellular matrix and a metazoan innovation 1, 2 that likely helped support the evolution of the three-dimensional body plan 3, 4. Structurally composed of polymeric laminin and crosslinked type IV collagen networks, the BM is a thin, dense, sheetlike material that provides structural support for epithelial and endothelial tissues and functions as a barrier limiting cellular movement [5]. However, specific
Cell Cycle Regulation of Invasion During Development
Invasive behavior is a critical component of metazoan development. This section reviews literature that suggests that the acquisition of invasive behavior during development is specifically regulated in a cell cycle-dependent fashion. During mammalian embryo implantation (Figure 1A), cytotrophoblasts, the first embryonic cell type to exhibit highly specialized functions, differentiate into extravillous trophoblasts, which then invade into the uterine lining, as the first step of placentation
Development and Cancer: Two Sides of the Same Coin
Cancer cells hijack developmental regulatory programs and signaling pathways to execute the suite of behaviors required for metastasis. Thus, the same morphogenetic cell biological behaviors and molecular cues that are required for developmental processes such as gastrulation and neural crest delamination during embryogenesis are also utilized by tumor cells to proliferate, communicate with the surrounding microenvironment, and adopt an invasive phenotype [47]. For processes like cell invasion,
Therapeutic Implications of Cell Cycle Regulation of Invasive Behavior
Traditional antineoplastic chemotherapeutics kill rapidly dividing cells. However, since invasive cells appear to exist in quiescent G1/G0 arrest (Table 1), these invasive, metastatic cell populations remain when the bulk of the tumor is killed by classical antineoplastics. For example, sublethal irradiation, which blocks the G1/S phase checkpoint, increases the metastatic potential of gliomas [98]. Further research is necessary to determine if cell cycle arrest triggered by sublethal doses of
Concluding Remarks
We have reviewed literature demonstrating that a broad array of cancers switch between invasive and proliferative states, with evidence ranging from correlative Matrigel invasion assays to histopathological studies of primary tumor samples (Table 1). Together, these data argue that cell cycle arrest may be a requirement for the acquisition of invasive activity. Given recent functional data from a developmental invasion event in C. elegans, we suggest that G1/G0 phase cell cycle arrest may be
Acknowledgments
The authors would like to thank Mathieu Boissan, R. Antonio Herrera, and Taylor Medwig for their feedback, as well as the two anonymous reviewers, whose comments greatly improved the manuscript. We also thank Taylor Medwig for confocal micrographs used in Figure 1. D.Q.M. is supported by the Carol M. Baldwin Foundation for Breast Cancer Research and by the National Institutes of Health, National Cancer Institute (R00-CA154870).
Glossary
- Basement membrane
- a dense highly crosslinked sheet of polymeric laminin and type IV collagen forming the substrate for endothelia and epithelia and providing a barrier function for most cells.
- Basement membrane invasion
- the process by which cells remove basement membrane allowing contact between cell layers or passage through the basement membrane.
- Caenorhabditis elegans anchor cell invasion
- an in vivo model system used to examine the process of basement membrane invasion, as a specialized somatic
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The C. elegans anchor cell: A model to elucidate mechanisms underlying invasion through basement membrane
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2023, Journal of Theoretical BiologyPML isoforms: a molecular basis for PML pleiotropic functions
2022, Trends in Biochemical SciencesCitation Excerpt :This model however, as all matters concerning PML, appears overly simplistic because beside inhibiting cell proliferation, PMLIV was found to promote cell migration and invasion in breast cancer and in glioblastoma [82,83], especially in conditions that mimic a metastasis-promoting tumor environment like exposure to TGF-β [84]. This observation is not surprising per se, considering that cancer dissemination requires a switch from a proliferative to an invasive state [85], but further underlines the complexity of PML biology. In addition, studies in different tumor models identified opposite functions for PMLI, which promotes proliferation in breast cancer cells [81] while inhibiting cell growth in glioblastoma [86].