At the crossroads: EGFR and PTHrP signaling in cancer-mediated diseases of bone.
The epidermal growth factor receptor is a well-established cancer therapeutic target due to its stimulation of proliferation, motility, and resistance to apoptosis. Recently, additional roles for the receptor have been identified in growth of metastases. Similar to development, metastatic spread requires signaling interactions between epithelial-derived tumor cells and mesenchymal derivatives of the microenvironment. This necessitates reactivation of developmental signaling molecules, including the hypercalcemia factor parathyroid hormone-related protein. This review covers the variations of epidermal growth factor receptor signaling in cancers that produce bone metastases, regulation of parathyroid hormone-related protein, and evidence that the two molecules drive cancer-mediated diseases of bone.
Medical Sciences, Indiana University School of Medicine, Bloomington, IN 47405, USA. jgfoley@indiana.edu
John
J
Foley
Nicole
N
Nickerson
David J
DJ
Riese
Peter C
PC
Hollenhorst
Gwendolen
G
Lorch
Anne M
AM
Foley
D017209:Apoptosis / Q000502:physiology; D001859:Bone Neoplasms / Q000556:secondary*; D002465:Cell Movement / Q000502:physiology; D049109:Cell Proliferation; D066246:ErbB Receptors / Q000235:genetics / Q000502:physiology*; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D006801:Humans; D010014:Osteolysis / Q000209:etiology; D044162:Parathyroid Hormone-Related Protein / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*
D044162:Parathyroid Hormone-Related Protein; D066246:ErbB Receptors