Hedgehog signalling in breast cancer

Kasper, Maria; Jaks, Viljar; Fiaschi, Marie; Toftgárd, Rune

doi:10.1093/carcin/bgp048

Cited by 132 publications

(107 citation statements)

References 127 publications

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“…However, such a threshold hypothesis is not likely for morphogens that are expected to act in response to low gradients of ligand. More likely, the low activity of HH signaling in plaques must constitute inhibition downstream of the primary HH receptor Patched (7,9). Smoothened antagonists can inhibit HH signal transduction downstream of Patched and are thus obvious candidates to participate in the HH signaling dichotomy.…”

Section: Resultsmentioning

confidence: 99%

“…On one hand, LDLs contribute to plaque formation, but on the other hand, they contribute to plaque stability by carrying antagonists of downstream HH signaling. It is important, however, to point out that other mechanisms, such as suppressor of fused (SUFU) expression (7,34), may also contribute to the functional dichotomy in HH signaling in the human vasculature. Disregarding the exact mechanism of HH signal transduction inhibition in atherosclerotic plaques, it is tempting to suggest that this inhibition constitutes an important antipathogenic signal and that enhanced knowledge of the mechanisms involved may contribute to better treatment and prevention of atherosclerotic disease.…”

Section: Resultsmentioning

confidence: 99%

“…HH constitutes a family of highly hydrophobic secreted morphogenetic hormones of which in humans three isoforms exist: Sonic (SHH), Indian (IHH) and Desert (DHH) (7). Their functions include maintenance of the endothelial compartment and orchestrating revascularization upon vessel occlusion-induced ischemia (8).…”

Section: Introductionmentioning

confidence: 99%

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Dichotomy in Hedgehog Signaling between Human Healthy Vessel and Atherosclerotic Plaques

Queiroz

Bijlsma

Tio

et al. 2012

Mol Med

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The major cause for plaque instability in atherosclerotic disease is neoangiogenic revascularization, but the factors controlling this process remain only partly understood. Hedgehog (HH) is a morphogen with important functions in revascularization, but its function in human healthy vessel biology as well as in atherosclerotic plaques has not been well investigated. Hence, we determined the status of HH pathway activity both in healthy vessels and atherosclerotic plaques. A series of 10 healthy organ donor-derived human vessels, 17 coronary atherosclerotic plaques and 24 atherosclerotic carotid plaques were investigated for HH pathway activity. We show that a healthy vessel is characterized by a high level of HH pathway activity but that atherosclerotic plaques are devoid of HH signaling despite the presence of HH ligand in these pathological structures. Thus, a dichotomy between healthy vessels and atherosclerotic plaques with respect to the activation status of the HH pathway exists, and it is tempting to suggest that downregulation of HH signaling contributes to long-term plaque stability.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

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Dichotomy in Hedgehog Signaling between Human Healthy Vessel and Atherosclerotic Plaques

Queiroz

Bijlsma

Tio

et al. 2012

Mol Med

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“…The exact role of activated Hh signaling in the development or progression of tumors remains to be elucidated. However, certain studies have indicated that Hh signaling plays a role in stem/progenitor cell maintenance and self-renewal, which is regarded as a significant marker of cancer stem cell (CSC) activation (19,20). Nevertheless, the role of this pathway in breast CSCs has yet to be determined.…”

Section: Introductionmentioning

confidence: 99%

Overexpression of Hedgehog signaling molecules and its involvement in triple-negative breast cancer

et al. 2011

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Abstract. The purpose of this study was to investigate the activation of Hedgehog (Hh) signaling molecules and its involvement in triple-negative breast cancer (TNBC). A total of 123 cases of paraffin blocks, including 83 cases of primary breast carcinoma, 30 cases of mammary hyperplasia and 10 cases of normal breast tissue, were immunohistochemically analyzed for Sonic Hedgehog (SHH), Patched-1 (PTCH1), Smoothened (SMO) and glioma-associated oncogene homoglog 1 (GLI1) expression. The expression of SMO and GLI1 in TNBC was significantly increased in comparison to non-triple-negative breast cancer (nTNBC). GLI1 expression manifested an inverse association with the estrogen receptor. The levels of GLI1 expression were increased in lymph nodepositive cases. The expression of SHH and SMO was increased in high histological grades. Furthermore, the expression of SMO and GLI1 was correlated with superior tumor stage. The expression of SHH, SMO and GLI1 was significantly increased in breast cancer and mammary hyperplasia. PTCH1 expression was significantly decreased in breast cancer compared to mammary hyperplasia and normal breast tissue. For the first time, clinical evidence has been provided in support of significant roles of Hh signaling in TNBC. Hh signaling is involved in breast ductal changes and malignant transformation. Measures to inhibit Hh activity may improve the prognosis of TNBC patients.

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“…Likewise, published literature supports the potential for the involvement of particular aspects of the hedgehog/Gli signaling pathway in other types of solid human tumors [11–16]. Here we will first address the nature of hedgehog signaling in normal and malignant cells and then describe the literature that suggests that hedgehog contributes to human prostate cancer.…”

mentioning

confidence: 95%

Targeting the CB2 cannabinoid receptor in osteoporosis

Chen

Carkner

Buttyan

2011

Expert Review of Endocrinology & Metabolism

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Hedgehog is a ligand-activated signaling pathway that regulates Gli-mediated transcription. Although most noted for its role as an embryonic morphogen, hyperactive hedgehog also causes human skin and brain malignancies. The hedgehog-related gene anomalies found in these tumors are rarely found in prostate cancer. Yet surveys of human prostate tumors show concordance of high expression of hedgehog ligands and Gli2 that correlate with the potential for metastasis and therapy-resistant behavior. Likewise, prostate cancer cell lines express hedgehog target genes, and their growth and survival is affected by hedgehog/Gli inhibitors. To date, the preponderance of data supports the idea that prostate tumors benefit from a paracrine hedgehog microenvironment similar to the developing prostate. Uncertainty remains as to whether hedgehog’s influence in prostate cancer also includes aspects of tumor cell autocrine-like signaling. The recent findings that Gli proteins interact with the androgen receptor and affect its transcriptional output have helped to identify a novel pathway through which hedgehog/Gli might affect prostate tumor behavior and raises questions as to whether hedgehog signaling in prostate cancer cells is suitably measured by the expression of Gli target genes alone.

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Hedgehog signalling in breast cancer

Cited by 132 publications

References 127 publications

Dichotomy in Hedgehog Signaling between Human Healthy Vessel and Atherosclerotic Plaques

Dichotomy in Hedgehog Signaling between Human Healthy Vessel and Atherosclerotic Plaques

Overexpression of Hedgehog signaling molecules and its involvement in triple-negative breast cancer

Targeting the CB2 cannabinoid receptor in osteoporosis

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