Although inflammation is a critical underlying factor in a range of diseases, including the progression of cancer, little is known about its role when normal cells become tumor cells. Now, scientists from the Florida campus of The Scripps Research Institute have shed new light on exactly how the activation of a pair of inflammatory signaling pathways leads to the transformation of normal breast cells to cancer cells.
The study, led by Jun-Li Luo, an assistant professor at Scripps Florida, was published online before print by the journal Molecular Cell.
The scientists’ discovery points to the activation of a self-sustaining signaling circuit that inhibits a specific RNA, a well-known tumor suppressor that helps limit the spread of cancer (metastasis). Therapies that disable this circuit and halt this miRNA repression could have the potential to treat cancer.
The Spark that Ignites Trouble
In the new study, scientists identified the specific pathways that transform breast epithelial cells into active cancer cells.
The researchers found immune/inflammatory cells ignite the transient activation of MEK/ERK and IKK/NF-kB pathways; the MEK/ERK pathway then directs a consistent activation of a signaling circuit in transformed cells. This consistent signaling circuit maintains the malignant state of the tumor cells.
Luo compares this process to starting a car—a car battery starts the engine much like the transient signal activation turns on the consistent signal circuit. Once the engine is started, it no longer needs the battery.
These new findings dovetail with the “multiple-hits theory” of tumor formation, which posits that once normal cells in the human body accumulate enough pre-cancerous mutations, they are at high-risk for transformation into tumor cells. While the newly described initial pathway activation is momentary and not enough to cause any lasting changes in cell behavior, it may be just enough to tip the cell’s transformation to cancer, especially if it comes on top of an accumulation of other cellular changes.