The Role of Hedgehog Pathway in Female Cancers

Garcia, Natália; Ulin, Mara; Al-Hendy, Ayman; Yang, Qiwei

doi:10.26502/jcsct.5079089

Cited by 11 publications

(7 citation statements)

References 84 publications

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“…The Hedgehog pathway is one of the key regulators involved in many biological events. Malfunction of this pathway is associated with various diseases, including several types of female cancers ( 427 ). An initial study demonstrated that elevated expression of SMO and GLI 1, the key members of the Hedgehog pathway, was observed in leiomyosarcoma relative to normal myometrium and uterine fibroid tumors.…”

Section: Future Perspectivesmentioning

confidence: 99%

Comprehensive Review of Uterine Fibroids: Developmental Origin, Pathogenesis, and Treatment

et al. 2021

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Uterine fibroids are benign monoclonal neoplasms of the myometrium, representing the most common tumors in women worldwide. To date, no long-term or non-invasive treatment option exists for hormone-dependent uterine fibroids due to the limited knowledge about the molecular mechanisms underlying the initiation and development of uterine fibroids. This paper comprehensively summarizes the recent research advances on uterine fibroids, focusing on their risk factors, development origin, pathogenetic mechanisms, and treatment options. Additionally, we describe the current treatment interventions for uterine fibroids. Finally, future perspectives on uterine fibroids studies are summarized. Deeper mechanistic insights into tumor etiology and uterine fibroids’ complexity can contribute to the newer targeted therapies.

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Section: Future Perspectivesmentioning

confidence: 99%

Comprehensive Review of Uterine Fibroids: Developmental Origin, Pathogenesis, and Treatment

et al. 2021

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“…GLI1 has only an activator form, while GLI2 and GLI3 have both activators (GLI2A and GLI3A) and repressor forms (GLI2R and GLI3R) [ 12 ]. GLI members act as the nuclear effectors at the end of the pathway, which is responsible for regulating the expression of downstream target genes [ 13 , 14 ].…”

Section: Introductionmentioning

confidence: 99%

Targeting Hedgehog Pathway and DNA Methyltransferases in Uterine Leiomyosarcoma Cells

Garcia

Al-Hendy

Baracat

et al. 2020

Cells

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Uterine leiomyosarcoma (LMS) is an aggressive tumor that presents a poor prognosis, high rates of recurrence, and metastasis. Because of its rarity, there is no information available concerning LMS molecular mechanisms of origin and development. Here, we assessed the expression profile of Hedgehog (HH) signaling pathway markers and the effects of their pharmacological inhibition on uterine smooth muscle (UTSM), leiomyoma, and LMS cells. Additionally, we also evaluated the effects of DNMTs inhibition on LMS cell behavior. Cell proliferation, migration and apoptosis rates were evaluated by MTT, Scratch, and Annexin V assays, respectively. RNA expression and protein levels were assessed by qRT-PCR and Western blot. We found that SMO and GLIs (1, 2, and 3) expression was upregulated in LMS cells, with increased nuclear levels of GLI proteins. Treatment with LDE225 (SMOi) and Gant61 (GLIi) resulted in a significant reduction in Glis protein levels in LMS (p < 0.05). Additionally, the expression of DNMT (1, 3a, and 3b), as well as GLI1 nuclear expression, was significantly decreased after treatment with HH inhibitor in LMS cells. Our results showed that blocking of SMO, GLI, and DNMTs is able to inhibit LMS proliferation, migration, and invasion. Importantly, the combination of those treatments exhibited a potentiated effect on LMS malignant features due to HH pathway deactivation.

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“…Several studies have previously shown that SMO inhibitors can be combined with other inhibitors or chemotherapeutic agents to effectively inhibit breast cancer progression ( 38-40 ). In particular, a clinical trial targeted SMO in the hedgehog signaling pathway in female patients with breast cancer ( 41 ). The results of these trials suggested that targeting this pathway can be an effective treatment option for patients with cancer ( 41 ).…”

Section: Discussionmentioning

confidence: 99%

“…In particular, a clinical trial targeted SMO in the hedgehog signaling pathway in female patients with breast cancer ( 41 ). The results of these trials suggested that targeting this pathway can be an effective treatment option for patients with cancer ( 41 ).…”

Section: Discussionmentioning

confidence: 99%

Expression of yes‑associated protein, β‑catenin and smoothened, and their clinical significance in invasive breast cancer

Zeng

Yang

2022

Exp Ther Med

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The expression profile and role of yes-associated protein (YAP) in occurrence and development of breast cancer is ambiguous. The present study aimed to explore the relationship among the YAP, β-catenin and smoothened (SMO) signaling pathways to provide a theoretical basis for the clinical diagnosis and treatment of invasive breast cancer. Immunohistochemistry was used to determine the protein expression levels of YAP, β-catenin and SMO in tumor, tumor-adjacent and normal breast tissue. The possible association between the expression levels of these three proteins and the clinicopathological features of patients with breast cancer was then analyzed by the χ 2 test. The protein expression of YAP was found to be downregulated, whilst β-catenin and SMO expression were found to be upregulated in tumor tissues as compared with that in normal breast tissues. In addition, the expression of YAP in breast cancer tissues was found to be associated with that of human epidermal growth factor receptor 2 (HER2), progesterone and estrogen receptors. By contrast, the protein expression of β-catenin and SMO in breast cancer tissues was only associated with HER2. There was a negative correlation between the expression of YAP and SMO protein in breast cancer tissues. Compared with that in the changes in each of YAP, β-catenin and SMO protein expression levels individually, their combined changes in expression were demonstrated to associate significantly with the tumor histological grade. To conclude, data from the present study suggest that the combined protein expression of YAP, β-catenin and SMO can be used as a prognostic indicator for the treatment of invasive breast cancer.

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The Role of Hedgehog Pathway in Female Cancers

Cited by 11 publications

References 84 publications

Comprehensive Review of Uterine Fibroids: Developmental Origin, Pathogenesis, and Treatment

Comprehensive Review of Uterine Fibroids: Developmental Origin, Pathogenesis, and Treatment

Targeting Hedgehog Pathway and DNA Methyltransferases in Uterine Leiomyosarcoma Cells

Expression of yes‑associated protein, β‑catenin and smoothened, and their clinical significance in invasive breast cancer

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