Cell cycle perturbation uncouples mitotic progression and invasive behavior in a post-mitotic cell
Michael A Q Martinez1, Chris Z Zhao1, Frances E Q Moore1
1Department of Biochemistry and Cell Biology, Stony Brook University, Stony Brook, NY, 11794, USA.
Differentiation; Research in Biological Diversity
|March 24, 2024
Summary
Cell cycle regulators like CKI-1 maintain the post-mitotic state in C. elegans anchor cells. Disrupting these regulators allows cells to proliferate while retaining invasive capabilities, bypassing the need for a post-mitotic state.
Area of Science:
- Cell Biology
- Developmental Biology
- Genetics
Background:
- The post-mitotic state is essential for differentiated cell functions during development.
- Mechanisms maintaining this state are not fully understood.
- The C. elegans anchor cell (AC) provides a model for studying post-mitotic cell invasion.
Purpose of the Study:
- Identify negative cell cycle regulators maintaining the AC's post-mitotic, invasive state.
- Investigate how cell cycle perturbation affects AC invasion.
- Understand the relationship between cell cycle status and invasive behavior.
Main Methods:
- Utilized C. elegans as a model organism for anchor cell invasion.
- Employed genetic screening to identify cell cycle regulators.
- Conducted time-lapse imaging to observe cell behavior.
- Analyzed gene regulatory networks controlling invasion.
Main Results:
- CKI-1 redundantly maintains the AC's post-mitotic state.
- Loss of CKI-1 with other regulators (CKI-2, LIN-35, FZR-1, LIN-23) caused ACs to proliferate.
- Proliferating ACs retained their invasive ability.
- Invasive behavior in proliferating cells was linked to sustained pro-invasive gene expression.
Conclusions:
- The post-mitotic state is critical for AC invasion, but can be bypassed.
- Multiple negative cell cycle regulators ensure the AC remains post-mitotic.
- Perturbing cell cycle control can decouple proliferation from invasion, maintaining invasive gene expression.
Related Concept Videos
The Cell Cycle Control System
2.9K
The cell cycle regulation directs how a cell proceeds from one phase to the next and begins mitosis. The cell cycle control system includes intracellular regulatory molecules and external triggers. They provide "stop" or "advance" signals and operate at specific cell cycle stages termed checkpoints to ensure that a particular process is completed before the cell advances to the next phase.
Cyclins and cyclin-dependent kinases (Cdks) are the primary cell cycle regulators and...
Cyclins and cyclin-dependent kinases (Cdks) are the primary cell cycle regulators and...
2.9K
Molecular Factors Affecting Cell Division
3.1K
Several external and internal factors influence the initiation and inhibition of cell division. For instance, the death of nearby cells or the release of human growth hormone (hGH) promotes cell division. In contrast, lack of hGH or crowding of cells can inhibit cell division.
Several proteins function as internal regulators to ensure each cell cycle stage is completed faithfully before proceeding to the next. Regulator molecules may act directly or influence the activity or production of other...
Several proteins function as internal regulators to ensure each cell cycle stage is completed faithfully before proceeding to the next. Regulator molecules may act directly or influence the activity or production of other...
3.1K
DNA Damage can Stall the Cell Cycle
9.1K
In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...
9.1K
Mitogens and the Cell Cycle
6.5K
Mitogens and their receptors play a crucial role in controlling the progression of the cell cycle. However, the loss of mitogenic control over cell division leads to tumor formation. Therefore, mitogens and mitogen receptors play an important role in cancer research. For instance, the epidermal growth factor (EGF) - a type of mitogen and its transmembrane receptor (EGFR), decides the fate of the cell's proliferation. When EGF binds to EGFR, a member of the ErbB family of tyrosine kinase...
6.5K
Inhibition of Cdk Activity
4.7K
The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
4.7K
Separation of Sister Chromatids
3.6K
At the transition from prophase to metaphase, there is a reduction in cohesion along the chromosomal arms, resulting in the resolution of sister chromatids. However, residual cohesin connections remain to hold the sister chromatids together until the transition from metaphase to anaphase. The residual connection prevents any premature separation of sister chromatids, blocking the risks of aneuploidy within the daughter cells.
At the onset of anaphase, separase, a proteolytic enzyme, is...
At the onset of anaphase, separase, a proteolytic enzyme, is...
3.6K


