Actin, which is a key component of the contraction apparatus of muscles and helps in movement also facilitates metastasis
A key protein that helps in movement also helps cancer cells spread, a new study found.
The protein is actin, a key component of the contraction apparatus of muscles throughout the body. It also helps cells make their crawling movements. The link between cell movement and signaling is through the cell’s actin cytoskeleton – chains of actin that dynamically assemble and disassemble to aid locomotion in cancerous and noncancerous cells.
Although the actin cytoskeleton was known to be involved in the spread, or metastasis, of cancer cells, the fact that the cell migration machinery can drive cancer cell growth has never before been described, said Dr. Gaudenz Danuser, UT Southwestern Chair of the Lyda Hill Department of Bioinformatics and Professor of Bioinformatics and Cell Biology. Dr. Danuser is the corresponding author of the study published today in Developmental Cell that identifies a novel role for actin in cell signaling.
The study demonstrates that form drives function in a mechanism that behaves one way in both noncancerous cells and in unstressed cancer cells but acts differently in cancer cells that encounter stressors such as chemotherapy or the need to adapt to a new environment such as after spreading from the skin to lung tissue
The study demonstrates that form drives function in a mechanism that behaves one way in both noncancerous cells and in unstressed cancer cells but acts differently in cancer cells that encounter stressors such as chemotherapy or the need to adapt to a new environment such as after spreading from the skin to lung tissue. When encountering such stresses, the actin mechanism affects signaling to promote drug resistance or aggressive metastatic growth.
In the paper, the researchers point out that drug resistance and metastasis represent “two of the most critical factors in determining prognosis for cancer patients.”
In their studies, the researchers took human skin cancer (melanoma) cells that contained a mutation in the Rac1 gene linked to chemotherapy-resistant tumors and used CRISPR/Cas9 gene editing to snip out the single-base pair mutation and revert it to the normal gene. The scientists found that in a petri dish, cells with the mutation continued to grow when exposed to chemotherapy, while cells with normal Rac1 could not – even though both kinds of cells remained cancerous. When injected into mice, cells carrying the mutation made much larger metastatic nodules than cells carrying the normal version of the gene. Interestingly, cancer cells with or without the mutation grew at the same rate, as long as they were not exposed to chemotherapy or remained in the primary tumors. Hence, it is the stress of a new environment that turns on cell growth in the mutated cells, the researchers said.
