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Melanoma: A Challenge
Melanoma, a highly malignant type of skin cancer, is a significant health concern globally, with a median survival of 6 to 10 months. Researchers are actively investigating the cell signaling mechanisms that can affect tumour growth. Recently, the Institute of Cancer Research, London, reported on a significant scientific discovery. Researchers grew cells in a bioengineered 3D cell matrix and depleted many genes simultaneously.

Employing robotic microscopy and sophisticated image analysis, they identified genes essential for regulating melanoma cell shape. Nine genes were identified that regulate cellular shape on soft materials and four that regulate cellular shape on stiff materials, enabling melanoma cells to invade a variety of different tissue types.

Depletion of ARHGEF9 led to a 48.7% increase in proportion of star-shaped cells and a 46.5% increase in proportion of spindle-shaped cells. On 2-dimensional matrices ARHGEF9 depletion led to flat, poorly contractile cells unable to form ameboid shapes.

They discovered that the melanoma cells use an ARHGEF9 gene for creating filopodia, finger-like projections that help melanoma cells attach to neighboring cellular structures providing 3-dimensional traction and enhancing metastasis. The filopodia promote integrin cluster activation, attachment, and protrusion stabilization. They may also enable melanoma cells to drill into collagen matrices.

Researchers now understand how melanomas harness the ARHGEF9 gene to become more invasive and are optimistic that devising a way to inhibit this process will prevent the formation of filopodia, thereby inhibiting metastasis.
Final Thoughts
The researchers anticipate that this discovery may open up avenues of research into the possible role of ARHGEF9 in other cancers.

Reference

Bousgouni, V., Inge, O., Robertson, D., Jones, I., Clatworthy, I., & Bakal, C. (2022). ARHGEF9 regulates melanoma morphogenesis in environments with diverse geometry and elasticity by promoting filopodial-driven adhesion. iScience, 25(8), 104795. https://doi.org/10.1016/j.isci.2022.104795

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