Hedgehog signaling pathway as a therapeutic target in various types of cancer

Onishi, Hideya; Katano, Mitsuo

doi:10.1111/j.1349-7006.2011.02010.x

Cited by 89 publications

(60 citation statements)

References 76 publications

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“…HH signaling in cancer Three major cancers have been identified that involve cell-autonomous hedgehog (HH) pathway over-activation: medulloblastoma (MB), rhabdomyosarcoma (RMS) and basal cell carcinoma (BCC) (Ng and Curran, 2011). Whereas BCC likely can arise from multiple adult skin stem cells gone rogue under the influence of aberrant HH (Wong and Reiter, 2011;Youssef et al, 2010), the other two cancer types have embryonic origins and are triggered by developmental defects in HH signaling (Onishi and Katano, 2011). The SHH subtype of MB, a highly prevalent childhood brain tumor originating in the cerebellum, is characterized by activation of the HH pathway, which accounts for one quarter of all MB cases (Remke et al, 2013).…”

Section: Teethmentioning

confidence: 99%

Roles for Hedgehog signaling in adult organ homeostasis and repair

2014

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The hedgehog (HH) pathway is well known for its mitogenic and morphogenic functions during development, and HH signaling continues in discrete populations of cells within many adult mammalian tissues. Growing evidence indicates that HH regulates diverse quiescent stem cell populations, but the exact roles that HH signaling plays in adult organ homeostasis and regeneration remain poorly understood. Here, we review recently identified functions of HH in modulating the behavior of tissue-specific adult stem and progenitor cells during homeostasis, regeneration and disease. We conclude that HH signaling is a key factor in the regulation of adult tissue homeostasis and repair, acting via multiple different routes to regulate distinct cellular outcomes, including maintenance of plasticity, in a context-dependent manner.

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Section: Teethmentioning

confidence: 99%

Roles for Hedgehog signaling in adult organ homeostasis and repair

2014

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“…Ectopic activation of the Hedgehog (HH) signaling pathway has been demonstrated to be involved in the initiation as well as the progression of prostate malignancy (3,6). The HH signaling pathway was first identified in Drosophila as a central organizer for proper embryonic patterning and development.…”

Section: Introductionmentioning

confidence: 99%

Inhibition of Gli1‑mediated prostate cancer cell proliferation by inhibiting the mTOR/S6K1 signaling pathway

Yang

Liu

et al. 2017

Oncol Lett

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Abstract. Ectopic activation of the canonical Hedgehog signaling pathway is involved in the development and progression of prostate cancer, which is one of the leading causes of cancer-associated mortality in males worldwide. However, the role of the non-canonical Hedgehog signaling pathway in prostate cancer remains generally unexplored. In the present study, it was identified that Gli (glioma-associated oncogene)1 and Gli2 were highly expressed at the protein level in the androgen-independent prostate cancer cell lines PC3 and DU145, but not in the androgen-dependent cancer cell line LNCaP. Silencing of Gli1 using small interfering RNA markedly decreased PC3 cell viability and liquid colony formation in vitro. The Gli1/2-specific inhibitor GANT61 markedly decreased cell viability by inducing cell apoptosis in PC3 and DU145 cells. GANT61 also alleviated liquid colony formation efficiency in PC3 and DU145 cells, suggesting that the activity of Gli1 is required for prostate cancer cell survival. To explore further the upstream signaling pathway involved in the regulation of Gli1 expression, it was identified that tumor necrosis factor α-triggered mammalian target of rapamycin (mTOR)/p70 ribosomal protein S6 kinase 1 (S6K1) activation was required for Gli1 expression. Pharmacological and genetic inhibition of S6K1 activation markedly decreased Gli1 and its downstream target gene mRNA expression. In addition, the phosphoinositide 3-kinase/mTOR inhibitor BEZ235 markedly decreased in vitro PC3 cell proliferation. The results of the present study indicate that the non-canonical Hedgehog pathway (mTOR/S6K1/Gli1) contributes to the development and progression of prostate cancer and that Gli1 is a potential therapeutic target in the treatment of prostate cancer.

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“…Although no physiologic SMO inhibitors have been identified so far, efforts to inhibit Hh pathway have been focused on this protein, considered the most druggable target of the pathway (38).…”

Section: Discussionmentioning

confidence: 99%