The oncogene cyclin D1 promotes bipolar spindle integrity under compressive force.
Renaldo Sutanto1, Lila Neahring1,2, Andrea Serra Marques1
1Department of Bioengineering & Therapeutic Sciences, University of California San Francisco, San Francisco, California, United States of America.
Plos One
|March 13, 2024
Summary
Oncogene cyclin D1 overexpression in cells creates abnormal mitotic spindles but protects them from fracturing under pressure. This may help cancer cells proliferate in mechanically stressful tumor environments.
Area of Science:
- Cell biology
- Cancer research
- Biophysics
Background:
- The mitotic spindle is crucial for chromosome segregation during cell division.
- Aberrant spindles are common in cancer, but their mechanical function in solid tumors is unclear.
- Oncogenic transformation's impact on spindle mechanics requires further investigation.
Purpose of the Study:
- To investigate the effects of cyclin D1 overexpression on mitotic spindle architecture.
- To assess how cyclin D1 affects spindle response to compressive force.
- To understand the role of cyclin D1 in cancer cell adaptation to mechanical stress.
Main Methods:
- Constitutive overexpression of the oncogene cyclin D1 in human MCF10A cells.
- Analysis of spindle architecture, including poles, centrioles, and chromosome number.
- Assessment of spindle pole integrity under applied compressive force.
Main Results:
- Cyclin D1 overexpression led to an increased incidence of multipolar spindles (extra poles, centrioles, chromosomes).
- Overexpressed cyclin D1 protected spindle poles from fracturing under compressive force.
- This protection was observed despite the increased incidence of multipolar divisions.
Conclusions:
- Cyclin D1 overexpression may confer a mechanical advantage to cells under compressive stress.
- This adaptation could contribute to cyclin D1's prevalence in cancers like breast cancer.
- The findings suggest a mechanism for cancer cell proliferation in mechanically challenging tumor microenvironments.
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