Protein Linked to Tissue Stiffness Found to Promote Breast Cancer Invasion and Metastatic Properties

Protein Linked to Tissue Stiffness Found to Promote Breast Cancer Invasion and Metastatic Properties
A study recently published in the journal Nature Cell Biology by researchers at the University of California, San Diego revealed a new molecular mechanism underlying the link between breast tissue stiffness, breast cancer aggressiveness and poor clinical outcome. The study is entitled “Matrix stiffness drives epithelial–mesenchymal transition and tumor metastasis through a TWIST1–G3BP2 mechanotransduction pathway.” Breast tumors are frequently detected by touch due to the formation of dense clusters of collagen fibers that render the tumor stiffer or harder in comparison with the surrounding tissue. Increased tumor stiffness is known to be linked to tumor progression, spread (metastasis) and poor survival rates. In order to assess the influence of tissue stiffness in tumor behavior, the research team used a hydrogel system that allowed them to vary the rigidity of 3D cultures of breast cells between a stiffness degree characteristic of normal mammary glands to the higher stiffness degree typical of breast tumors. The team found that under conditions of high stiffness, a protein known as TWIST1 loses its molecular anchor, a protein called G3BP2, and travels from the cytoplasm into the cell’s nucleus. Once in the nucleus, TWIST1 activates genes that allow breast cancer cells to invade the surrounding healthy tissue and to metastasize into other parts of the body. “We’re finding that cancer cell behavior isn’t driven by just biochemical signals, but also biomechanical signals from the tumor’s physical environment,” said the study’s senior author Dr. Jin
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