Representative images of a WM983B melanoma cell nucleus with a nuclear envelope bleb stained for Lamin A/C (green), Lamin B1 (magenta) and DNA (blue). Scale bar, 10 μm. Credit: Jung Garcia, et al.
Key points:
- Researchers identify a protein that makes certain skin cancers more aggressive.
- The study found aggressive melanoma cells could change the shape of their nucleus to overcome physical constraints.
- The team plans to investigate whether nuclear envelope blebbing occurs in other types of cells.
New research has identified a protein that makes melanoma aggressive by giving its cancer cells the ability to change the shape of their nucleus, which allows the cells to migrate and spread around the body.
The study, published in Nature Cell Biology, modeled the behavior of aggressive melanoma cells that are able to change the shape of their nucleus to overcome the physical constraints that cancer cells encounter when they migrate through tissues.
In a study co-led by Victoria Sanz-Moreno and Jeremy Carlton, a team of researchers challenged aggressive and less aggressive melanoma cells in laboratory experiments to migrate through pores in an artificial membrane that were smaller than their own nucleus. The aggressive cells were from a site of metastasis in a patient with melanoma, and the less aggressive cells were from the original or "primary" melanoma tumor of the same patient.
Imaging conducted after the migration experiments showed that the aggressive cells were able to move through the pores more effectively than the less aggressive ones by forming bulges at the edge of their nucleus, called "blebs." Genetic analyses of the melanoma cells revealed that the aggressive cells that formed the blebs contained higher levels of the LAP1 protein, which sits within the nucleus’s membrane.
The team also observed the LAP1 levels were higher in tissue samples taken from sites of metastasis in melanoma patients compared to the levels found in primary tumors. The patients that had high levels of LAP1 in the cells around the edge of the primary tumor had more aggressive cancer and poorer outcomes.
“Melanoma is the most aggressive and deadly type of skin cancer. By combining the expertise of my laboratory with that of Dr Carlton’s, we have gained new mechanistic understanding of how LAP1 contributes to melanoma progression, and have shown that LAP1 is a key regulator of melanoma aggressiveness in laboratory and patient models,” said Sanz-Moreno.
The team now plans to investigate whether nuclear envelope blebbing driven by LAP1 occurs in other cells that make up a tumor to determine if they help or hinder the progression of cancer.