 A cytoskeletal protein might be involved in promoting breast cancer by making cancer cells acquire some features of stem cells. Researchers have found that fassin, a protein that bundles together the actin filaments that serve as the backbone of cells, is important for keeping breast cancer stem cells alive. The results shed light on what is going on inside cells as they break from normalcy to become cancerous, and highlight fassin as a potential diagnostic marker and therapeutic target. One reason why cancer can be so hard to treat is that certain tumor cells are resistant to chemotherapy and can sell for new, providing an endless supply of cells to reseed tumors. They're known as cancer stem cells because they hijack several properties of stem cells, like expressing transcription factors that allow for cell renewal to push their cancerous agenda. Fassin is found in higher amounts in tumors and has been linked to breast cancer chemoresistance and spread. Two key features of cancer stem cells, raising the possibility that this protein might promote cancer by regulating cancer stem cells. To find out if that's the case, researchers first experimentally lowered the amount of fassin in a human breast cancer cell line. When treated with chemotherapy, they found that these cells died more readily than those with the protein. The surviving cells, which were more common among cells with fassin, were more likely to be cancer stem cells, expressing high levels of certain markers. The reverse experiment, giving cells extra fassin, allowed more cells to survive chemotherapy and increased the number of apparent stem cells. When the scientists checked for stem cell-related transcription factors, they saw a similar trend. The cells without fassin had reduced amounts of cell renewal factors, while cells with extra fassin had higher amounts. The researchers then looked to see if fassin was associated with cancer cell invasion and spread. As cancer cells prepared to spread, they become more spindle-shaped and mobile. In a cell model of this transition, scientists found that fassin levels increased, while removing fassin reversed this process. Fassin was also found to be critical for tumor formation in the Petri dish, strongly supporting fassin's role in regulating cancer stem cells. But the real test is whether fassin can help cells self-renew and create tumors in animals. To find out, researchers injected small doses of breast cancer cells into mice with compromised immune systems. Just 50 cells with fassin were needed to produce tumors in a third of the mice. Without fassin, though, none of the mice developed tumors with so few cells. How might fassin be doing all this? Notch is an important signaling pathway that controls cell fate in the breast. The scientists found that in cells without fassin, notch signaling was low, and that that signaling was necessary for robust tumor formation in the Petri dish. In fact, blocking notch signaling made cells with fassin behave as if they didn't have the protein. They were less able to form tumors and more likely to die after chemotherapy. The findings suggest that fassin makes it easier for cancer stem cells to form tumors and stay alive by activating the notch cell for neural pathway. Paying attention to fassin levels in patients might be a valuable way of monitoring cancer and personalizing therapy. And one day, targeting fassin with a drug, in combination with other chemo, might even provide a more effective way to treat the disease.