ErbB2 Makes β4 Integrin an Accomplice in Tumorigenesis

ogy. For example, how is expression of ephrinB2 and EphB4 regulated? Is their expression regulated by systemic factors or local factors that modulate bone remodeling? What is their relationship to common signaling pathways and other important genes involved in osteoclast and osteoblast differentiation? What is their relationship to the other molecular mechanisms proposed for coupling, including growth factors, and are these mechanisms mutually exclusive? Is this a common pathway utilized by all regulators of bone remodeling? Do cancer cells use similar bidirectional mechanisms to survive, proliferate, and/or use these mechanisms to cause the aberrations in osteoclast/osteoblast coupling that are characteristic of osteolytic and osteoblastic bone metastasis? The results of this provocative study have certainly provided the foundation for many new studies in this complex field.