New research published in the Journal of Cell Biology uncovers how a sticky protein called fibronectin promotes the activity of estrogen in breast cancer cells. The researchers show a novel mechanism of estrogen receptor signaling that is regulated by fibronectin. They found that exposure to fibronectin prolongs the activity of estrogen receptors in breast cancer cells.
The hormone estrogen plays a key role in the development of healthy cells and, in many cases, cancerous cells. Estrogen attaches to cellular estrogen receptors, which promote cell growth and survival. But too much estrogen receptor activity can cause cells to proliferate rapidly, leading to tumor growth. About 75% of breast cancers are considered estrogen receptor positive because estrogen causes those cancers to propagate, author notes.
As cancerous cells start to invade into surrounding tissue, they encounter the gluey fibronectin protein. "In the normal mammary gland, epithelial cells are not in contact with fibronectin," author explains. Fibronectin is part of the extracellular matrix, the meshwork of proteins and molecules that surrounds cells. In tumors, the production of this surrounding network often becomes unregulated. Previous research has shown that high levels of fibronectin and its receptor β1-integrin correlate with lower breast cancer survival, but it was not known why.
In the current study, scientists discovered that fibronectin boosts estrogen receptors' activity in breast cancer cells. They found that when breast cancer cells are surrounded by fibronectin, estrogen receptors avoid destruction by lysosomes--cellular garbage disposal units--and can continue to drive cancer cell growth. ERα+ vesicles are present within human breast tissues, and colocalization with β1-integrin is detected primarily in tumors. "This would allow breast cancer cells to become resistant to common endocrine therapy drugs that target the receptor," author says.
Their research suggests that therapeutics that interfere with fibronectin's influence on the estrogen receptor could help treat drug-resistant breast cancers. This work also reveals how the meshwork of proteins surrounding tumors can influence cancer progression.
Role of extracellular matrix protein in breast cancer growth
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