By Snigdha Kanadibhotla ‘21

Fundamentally rooted in a lack of cell cycle control, cancer is predicted to affect 38.4% of Americans within their lifetimes (1). While most healthy cells are regulated by three cell cycle checkpoints, cancerous cells can bypass these regulatory systems, which leads to uncontrolled division and metastasis (the spread of cancer through the body). Considered to be a unique characteristic of cancer, metastasis can only occur when cells invade the basement membrane, a barrier that separates different tissues. However, another class of healthy cells – embryonic cells in developing fetuses – have also been shown to break through the basement membrane during morphogenesis, a process during which cells organize themselves into a three dimensional body plan. Given that these two cell types undergo similar processes, it is possible that there are analogous mechanisms in both cell types that facilitate basement membrane interactions. Investigating these similarities may lead to the development of future therapeutics.

To test the links between cancer and embryonic cells, Dr. David Matus et al. studied anchor cells (a type of embryonic cell) in the nematode C. Elegans (2). From this model, it was found that there was increased expression of genes critical for invasion during the G1/G0 phase of the cell cycle, suggesting that anchor cells had to be arrested in this phase to penetrate the basement membrane (3). Another study conducted by Qian et al. found that breast cancer cells must express the gene p21CIP1, which is associated with the G1/G0 phase, in order to metastasize (4). This indicates that breast cancer cells and embryonic cells share a similar reliance during this cell cycle phase.

Though this study presents strong evidence linking characteristics of embryonic and cancer cells, further research must now be done to identify the specific biomolecular mechanisms responsible for the metastasis processes, including G1/G0 arrest. In concert, these investigations could lead to the development of novel cancer therapeutics for preventing metastasis.

References

1. Cancer Statistics. National Cancer Institute, http://www.cancer.gov/about-cancer/understanding/statistics  
2. A. Kohrman, D. Matus, Divide or conquer: cell cycle regulation of invasive behavior. Trends in Cell Biology 27, 12–25 (2017).  
3. D. Matus, et. al., Invasive cell fate requires G1 cell-cycle arrest and histone deacetylase-mediated changes in gene expression. Developmental Cell 35, 162-174 (2015).  
4. X. Qian, et. al., p21CIP1 mediates reciprocal switching between proliferation and invasion during metastasis. Oncogene 32, 2292–2303 (2013).  
5. Image retrieved from: https://www.cancer.gov/about-cancer/understanding/what-is-cancer