The Role of Physical Environment in Genetic Changes

Scientists have traditionally believed that genetic changes occur due to internal cellular processes that cause DNA and histone proteins to be tagged, such as methylation or acetylation. However, a new study led by Richard White and Miranda Hunter has revealed that the physical environment surrounding cells plays a crucial role in triggering genetic transformations.

Environmental Impact on Cancer Cells

Using a zebrafish model to study melanoma, the researchers demonstrated that cancer cells, when exposed to physical pressure from surrounding tissues, undergo structural and functional changes. Instead of rapid division, the cells activate a ‘neural invasion’ program, allowing them to migrate and spread into adjacent tissues.

This finding highlights the significant role of the physical environment in altering cancer cell behavior, emphasizing the importance of understanding environmental factors in developing new treatments.

The Role of HMGB2 Protein in Genetic Transformations

At the core of this transformation is the HMGB2 protein, which responds to mechanical stress by binding to chromatin and altering how genetic material is packaged. This exposure of specific genome regions associated with invasion makes them available for gene expression.

Cells with high levels of HMGB2 become less proliferative but more invasive and resistant to treatment, complicating cancer therapy.

Restructuring the Internal Cell Framework

The study also showed that melanoma cells adapt to external pressure by restructuring their internal framework, forming a cage-like structure around the nucleus. This protective shield includes the LINC complex, a molecular bridge linking the cytoskeleton to the nuclear membrane, helping protect the nucleus from stress-induced rupture.

This discovery underscores how physical stresses can be a powerful and underestimated force in driving genetic changes.

Therapeutic Challenges and Scientific Pursuits

White explained that cancer cells can rapidly switch between different states based on signals from their environment. This switching, which can be triggered by mechanical forces within the tumor microenvironment, presents a significant challenge for treatment.

By identifying the factors involved in this transformation, researchers hope to develop therapies that prevent or even reverse the invasive transformation of cells.

Conclusion

The study highlights the crucial role of the surrounding environment in shaping cancer cell behavior, illustrating how physical signals can drive cells to reorganize their cytoskeletal and nuclear structures and genetic packaging to transition between growth and invasion states. This new understanding opens the door to innovative therapeutic strategies targeting the environmental factors influencing cancer cell transformation.