La voie de signalisation PATCHED/Sonic Hedgehog dans le cancer superficiel de la vessie

LaRue, Hélène; Simoneau, Maryse; Aboulkassim, Tahar; Lemieux, Patricia; Girard, Johanne; Hamed, Sahar; Hovington, Hélène; Fradet, Yves

doi:10.1051/medsci/20031910920

Cited by 4 publications

(3 citation statements)

References 20 publications

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“…Patched 1 (Ptch1) mutation in patients with Gorlin’s syndrome shows early onset of multiple basal cell carcinoma 18 and medulloblastoma 19 . Aberrant Shh expression has been reported in lung 20 , bladder 21 , colorectal 22 , pancreatic 23 and prostate 24 cancer. Shh has been thought to play a critical role in carcinogenesis and metastasis in breast cancers.…”

Section: Discussionmentioning

confidence: 99%

Overexpression of sonic hedgehog in the triple negative breast cancer: clinicopathological characteristics of high burden breast cancer patients from Bangladesh

Noman

Uddin

Rahman

et al. 2016

Sci Rep

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Dysregulation of Hedgehog (Hh) signaling pathway has been documented in mammary gland development and breast cancer (BC) progression. Despite the remarkable progress in therapeutic interventions, BC related mortality in Bangladesh increased in the last decade. Triple negative breast cancer (TNBC) still presents a critical therapeutic challenge. Thus effective targeted therapy is urgently needed. In this study, we report the clinicopathological characteristics and prognosis of BC patients from Bangladesh. Routine immunohistochemical analysis and high throughput RNA-Seq data from the TCGA library were used to analyze the expression pattern and association of high and low level of Shh expression in a collection of BC patients with a long-term follow-up. High levels of Shh were observed in a subset of BC tumors with poor prognostic pathological features. Higher level of Shh expression correlated with a significantly poorer overall survival of patients compared with patients whose tumors expressed a low level of Shh. These data support the contention that Shh could be a novel biomarker for breast cancer that is involved in mediating the aggressive phenotype of BC. We propose that BC patients exhibiting a higher level of Shh expression, representing a subset of BC patients, would be amenable to Shh targeted therapy.

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Section: Discussionmentioning

confidence: 99%

Overexpression of sonic hedgehog in the triple negative breast cancer: clinicopathological characteristics of high burden breast cancer patients from Bangladesh

Noman

Uddin

Rahman

et al. 2016

Sci Rep

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“…Of the three, Shh is the most widely studied and closely associated with breast cancer. [11] It has been found that there is an abnormally high expression of Shh in lung cancer, [12] bladder cancer, [13] colorectal cancer, [14] pancreatic cancer, [15] prostatic cancer [16] and other tumors. It is confirmed that the abnormal expression of SHH plays a key role in the occurrence and development of breast cancer.…”

Section: Expression and Significance Of Shh In Triple-negative Breast...mentioning

confidence: 99%

Expression and significance of Shh, Gli1 and β-catenin in triple-negative breast cancer tissues

Wang¹,

Zhang

2023

DCC

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Objective: To detect the expression of Shh, Gli1 and β-catenin in triple negative breast cancer tissues and paracancer breast tissues by qRT-PCR and immunohistochemistry and to analyze their correlation with clinicopathological features.Methods: (1) qRT-PCR was used to detect the mRNA expression of Shh, Gli1 and β-catenin in 30 cases of triple negative breast cancer and their paracancer breast tissues, and the correlation among them was analyzed. (2) The expression of Shh, Gli1 and β-catenin proteins in 30 triple negative breast cancer and their paracancer breast tissues was detected by immunohistochemistry, and their correlation with clinicopathological features was analyzed.Results: (1) Shh mRNA expression (1.2334 ± 0.27867), Gli1 mRNA expression (1.2135 ± 0.20636) and β-catenin mRNA expression (1.1421 ± 0.32330) in triple negative breast cancer tissues were higher than that in paracancer breast tissues, i.e., Shh mRNA expression (1.0022 ± 0.06721), Gli1 mRNA expression (1.0003 ± 0.02420) and -catenin mRNA expression (1.0033 ± 0.07920) were significantly different (p < .05). There was a significantly positive correlation between the mRNA expression of Shh and Gli1 (r = .989, p < .001), and between the mRNA expression of Shh and β-catenin (r = .868, p < .001). There was a significantly positive correlation between the mRNA expression of Gli1 and β-catenin expression (r = .869, p < .001). (2) The positive expression rates of Shh, Gli1 and β-catenin in triple negative breast cancer tissues were 93.3% (28/30), 96.7% (29/30) and 93.3% (28/30), respectively, which were higher than those in paracancer tissues 60% (18/30), 73.3% (22/30) and 73.3% (22/30), the differences were statistically significant (p < .05). There was a significantly positive correlation between the mRNA expression of Shh and Gli1 (r = .958, p < .001), and between the mRNA expression of Shh and β-catenin (r = .952, p < .001). There was a significantly positive correlation between the mRNA expression of Gli1 and β-catenin expression (r = .927, p < .001). The expression of Shh, Gli1 and β-catenin protein in triple negative breast cancer was not correlated with age and tumor size (p > .05), but Shh was positively correlated with histological grade (G) (r = .774, p < .001). Furthermore, Gli1 was positively correlated with histological grade (r = .757, p < .001). β-catenin was positively correlated with histological grade (r = .739, p < .001). Shh was positively correlated with TNM staging (r = .460, p = .010). Gli1 was positively correlated with TNM staging (r = .414, p = .023). -catenin was positively correlated with TNM staging (r = .404, p = .027). Shh was positively correlated with lymph node metastasis (r = .540, p = .002). Gli1 was positively correlated with lymph node metastasis (r = .515, p = .004). β-catenin was positively correlated with lymph node metastasis (r = .559, p = .001).Conclusions: (1) The up-regulated expression of Shh, Gli1 and β-catenin proteins in triple negative breast cancer suggests that Shh, Gli1 and β-catenin proteins are involved in tumor genesis. The combined detection of the three proteins may provide a theoretical basis for the diagnosis and prognosis evaluation of triple negative breast cancer. (2) Shh was positively correlated with Gli1 protein expression and β-catenin protein expression. Gli1 was positively correlated with β-catenin protein expression, suggesting that the three types of proteins play a synergistic role in the occurrence and development of TNBC. There may be crosstalk in the Wnt/β-catenin and Hedgehog signaling pathways in TNBC, which may provide a new approach for the treatment of TNBC. (3) The expression of Shh, Gli1 and β-catenin proteins was correlated with the degree of differentiation, TNM staging and lymph node metastasis of triple negative breast cancer, but not correlated with age and tumor size. Therefore, it was predicted that the three types of proteins were related to the invasion, metastasis and prognosis of TNBC.

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“…L'activation constitutive de la voie HH est associée au développement de nombreuses pathologies graves autres que les CBC, ce qui explique que le GDC-0449 représente un grand espoir thérapeutique. Cet inhibiteur a également été testé pour traiter un patient atteint d'un cas extrême de médulloblastome réfractaire à toute thérapie [10], et des essais cliniques pourraient être proposés dans le traitement de cancers colorectaux métastatiques et de cancers ovariens avancés [13]. La voie HH est impliquée dans de nombreux processus biologiques au cours de l'organogenèse.…”

Section: L'activation Constitutive De La Voie Hedgehog Dans La Peau Iunclassified

Les inhibiteurs de la voie Hedgehog

Vidal

2010

Med Sci (Paris)

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La voie de signalisation PATCHED/Sonic Hedgehog dans le cancer superficiel de la vessie

Cited by 4 publications

References 20 publications

Overexpression of sonic hedgehog in the triple negative breast cancer: clinicopathological characteristics of high burden breast cancer patients from Bangladesh

Overexpression of sonic hedgehog in the triple negative breast cancer: clinicopathological characteristics of high burden breast cancer patients from Bangladesh

Expression and significance of Shh, Gli1 and β-catenin in triple-negative breast cancer tissues

Les inhibiteurs de la voie Hedgehog

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