Paracrine pathway activities are being increasingly recognized as instrumental regulatory mechanisms of epithelial-stromal interactions that play important roles in physiological and pathological self-renewal of stem cells and in the initiation and maintenance of neoplastic tumor development. Stromal-specific Hedgehog (Hh) responses and epithelial-associated Wnt pathway activities have been recently appreciated as important factors in stem cell self-renewal and carcinogenesis. Furthermore, Hh and Wnt pathways frequently crosstalk with each other to regulate the growth of epithelial cells in a context-dependent manner. Because small molecule modulators of Hh and Wnt pathway activities are readily available, emerging roles of Hh-Wnt pathway crosstalk in epithelial-stromal interactions will shed light on the development of regenerative and anticancer medicines.
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