Hedgehog Signaling for Urogenital Organogenesis and Prostate Cancer: An Implication for the Epithelial–Mesenchyme Interaction (EMI)

Abstract

Hedgehog (Hh) signaling is an essential growth factor signaling pathway especially in the regulation of epithelial–mesenchymal interactions (EMI) during the development of the urogenital organs such as the bladder and the external genitalia (EXG). The Hh ligands are often expressed in the epithelia, affecting the surrounding mesenchyme, and thus constituting a form of paracrine signaling. The development of the urogenital organ, therefore, provides an intriguing opportunity to study EMI and its relationship with other pathways, such as hormonal signaling. Cellular interactions of prostate cancer (PCa) with its neighboring tissue is also noteworthy. The local microenvironment, including the bone metastatic site, can release cellular signals which can affect the malignant tumors, and vice versa. Thus, it is necessary to compare possible similarities and divergences in Hh signaling functions and its interaction with other local growth factors, such as BMP (bone morphogenetic protein) between organogenesis and tumorigenesis. Additionally, this review will discuss two pertinent research aspects of Hh signaling: (1) the potential signaling crosstalk between Hh and androgen signaling; and (2) the effect of signaling between the epithelia and the mesenchyme on the status of the basement membrane with extracellular matrix structures located on the epithelial–mesenchymal interface.