Hedgehog signalling in cancer formation and maintenance

Activation of the hedgehog pathway confers a poor prognosis in embryonal and fusion gene-negative alveolar rhabdomyosarcoma

“…Gli1 and Ptch1 are pivotal markers of ongoing active Hh signaling (Ruiz i Altaba et al, 2002; Pasca di Magliano and Hebrok, 2003). Although both genes have previously been shown to be expressed in human RMS at higher levels than in normal muscle (Tostar et al, 2006), the question as to whether Hh signaling is differentially activated in distinct subsets of RMS has not been previously addressed.…”

“…The hedgehog (Hh) pathway is an evolutionally highly conserved signaling cascade, which has a nonredundant function in the control of many developmental processes and has also been implicated to contribute to cancer formation and progression (Ruiz i Altaba et al, 2002;Pasca di Magliano and Hebrok, 2003). Within this pathway, Patched1 (Ptch1) together with smoothened (Smo) forms a receptor complex for Hh.…”

“…Distinct mutations in key components of the Hh signaling cascade, for example, mutations in Ptch1, have been identified in human cancers that result in pathological activation of the Hh pathway (Pasca di Magliano and Hebrok, 2003;Scales and de Sauvage, 2009). In addition to genetic alterations, ligand-dependent stimulation of Hh signaling has recently been shown to promote tumor cell growth in different types of human cancers (Berman et al, 2002Thayer et al, 2003;Watkins et al, 2003;Karhadkar et al, 2004;Scales and de Sauvage, 2009).…”

Activation of the hedgehog-signaling pathway in human cancer and the clinical implications

“…Studies also indicate that Hh signaling may be involved in different stages of carcinogenesis in different tumors. In pancreatic and esophageal cancers for example, activation of this pathway is found in both early tumors and metastatic cancer (Bailey et al, 2009;Feldmann et al, 2008;Ma et al, 2006;Pasca di Magliano and Hebrok, 2003), suggesting that Hh signaling has a significant role in carcinogenesis of these tumors. In support of these findings, transgenic mice with pancreatic-specific expression of SHH or (Sheng et al, 2004).…”

Cooperation between GLI and JUN enhances transcription of JUN and selected GLI target genes

“…The importance of the HH/GLI pathway and its components in regulating proliferation and differentiation is reflected in the growing number of malignancies of skin, brain, pancreas, prostate and lung, which have been linked to ectopic expression of activator GLI proteins (reviewed in Evangelista et al, 2006;Hebrok, 2003;Pasca di Magliano and Hebrok, 2003;Rubin and de Sauvage, 2006;Ruiz i Altaba et al, 2007;Stecca and Ruiz i Altaba, 2002;Vezina and Bushman, 2007). Normally, binding of HH to its receptor PTCH leads to the stabilization and activation of full-length GLI proteins (GLIact) through the transmembrane signal transducer smoothened (SMOH).…”