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Does Superfamily of Motor Proteins Play a Role in Invasive Melanoma?

By: Lauren Harrison, MS
Posted: Tuesday, March 5, 2019

In a new article published in Cell, a team of researchers report that the interaction between Rho-associated protein kinase (ROCK) and myosin II is largely responsible for the rounded-amoeboid migration during metastatic dissemination in melanoma. Victoria Sanz-Moreno, PhD, of King’s College London, and colleagues reported the activity of ROCK-myosin II in reprogramming the innate immune microenvironment to support tumor growth.

“This study highlights how cancer cells interact with and influence their surrounding environment to grow and spread,” explained Dr. Sanz-Moreno in an institutional press release.

The team utilized a total of 47 human melanoma biopsies to perform their experiments. Cells with high levels of myosin II activity were found to be on the invasive fronts of primary tumors, in proximity to tumor-associated macrophages and vessels. Through proteomic analysis, ROCK-myosin II activity was found to control an immunomodulatory secretome, releasing cytokines, chemokines, and growth factors. Among the effects of the secretome is both recruitment of monocytes and promotion of their subsequent activation into macrophages. The combination of these melanoma cancer cells and macrophages encourages the formation of abnormal vessel growth, further driving tumor growth.

Additional analysis revealed that ROCK-myosin II promotes the release of interleukin-1α and nuclear factor kappa light chain enhancer of activated B cells (NF-κB) activation in melanoma cells. This interaction supports the secretory phenotype in a positive feedback loop. Upon depletion or inhibition of ROCK-myosin II activity, researchers saw a reduction in amoeboid behavior, secretion of interleukin-1α, and NF-κB activation in melanoma cells.

“By using therapeutic drugs that block either myosin II activity or the release of interleukin-1α, we can make the tumor less invasive and slow its growth, making it easier to treat,” proposed Dr. Sanz-Moreno.

Disclosure: The study authors’ disclosure information may be found at cell.com.



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