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Figure 2. The multifunctional role of Notch signaling in multiple myeloma (MM). MM cells exhibit increased expression of Notch components that help them to receive and transmit near-range signals from and to adjacent cells. Homotypic Notch communication between MM cells increases MM cell proliferation. Tumor growth is further supported by Notch signals received by stromal cells and osteocytes. In addition, MM cells enhanced angiogenesis via sending pro-angiogenic Notch signals to endothelial cells, stromal cells, and osteocytes. The increased angiogenesis in turn aids tumor growth by providing nutrients to the tumor. Both homotypic and heterotypic (from stromal cells) Notch signals confer drug-resistance to MM cells and promote MM cell survival. Moreover, Notch signals from and to bone cells contribute to the progression of the MM-induced osteolytic bone disease.