Prostate cancer and Hedgehog signalling pathway

Abstract

The Hedgehog (Hh) family of intercellular signalling proteins have come to be recognised as key mediators in many fundamental processes in embryonic development. Their activities are central to the growth, patterning and morphogenesis of many different regions within the bodies of vertebrates. In some contexts, Hh signals act as morphogens in the dose-dependent induction of distinct cell fates within a target field, in others as mitogens in the regulation of cell proliferation or as inducing factors controlling the form of a developing organ. These diverse functions of Hh proteins raise many intriguing questions about their mode of action. Various studies have now demonstrated the function of Hh signalling in the control of cell proliferation, especially for stem cells and stem-like progenitors. Abnormal activation of the Hh pathway has been demonstrated in a variety of human tumours. Hh pathway activity in these tumours is required for cancer cell proliferation and tumour growth. Recent studies have uncovered the role for Hh signalling in advanced prostate cancer and demonstrated that autocrine signalling by tumour cells is required for proliferation, viability and invasive behaviour. Thus, Hh signalling represents a novel pathway in prostate cancer that offers opportunities for prognostic biomarker development, drug targeting and therapeutic response monitoring.

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“…Recently, dysregulated activation of SHH signaling has been observed in small cell lung cancer [12], pancreatic carcinoma [13], prostate cancer [14], and gastric cancer [15,16].…”

Cancer Stem Cells in Breast: Current Opinion and Future Challenges

“…They called this cell population cancer stem cells (CSC) [1] . Since then, putative CSC have been isolated from many other tumors including breast, brain, colon, pancreas, prostate, lung and head and neck tumors [2][3][4][5][6][7][8][9] .…”

Novel strategies targeting cancer stem cells through phytochemicals and their analogs

“…Enhanced Hedgehog signaling was found to be associated with progression and acceleration of prostate cancer. Recent experiments have shown important role of Hedgehog signaling in prostate cancer, and autocrine Hedgehog signaling by tumor cells is required for proliferation, viability, and invasive behavior of prostate cancer [141]. It has been shown that activation of Hedgehog signaling is involved in CSCs and EMT features in several types of cancers including colon, gastric, esophagus, hepatic, and other cancers [142–146].…”