TNF and cancer: Gap junctions formed between breast/lung cancer and astrocytes assist cancer cells to transfer cGAMP to astrocytes, produce cytokines such as tumor necrosis factor and interferon-α, activate the STING pathway, and further stimulate NF-κB and STAT1 signaling in brain metastatic cells via paracrine; consequently, cancer growth and resistance to chemotherapy are promoted.125,126 In breast-to-brain metastasis, pseudo-tripartite synapses are generated between cancer cells and neurons.