Comprehensive immunohistochemical analyses on expression levels of hedgehog signaling molecules in breast cancers

Kurebayashi, Junichi; Kanomata, Naoki; Koike, Yoshikazu; Ohta, Yusuke; Saitoh, Wataru; Kishino, Emi

doi:10.1007/s12282-018-0884-2

Cited by 10 publications

(8 citation statements)

References 21 publications

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“…The study revealed higher SHH immunoexpression in well-differentiated tumors than in poorly differentiated tumors, which is a similar result to the current findings for SHH mRNA expression and ccRCC grade ( 54 ). However, in breast cancer tissues, the immunoreactivity of SHH, GLI1 and GLI2 was found to be positively associated with histological grade ( 55 ), which may suggest different tendencies in the expression of SHH signaling genes depending on cancer type and histological grade.…”

Section: Discussionmentioning

confidence: 99%

Expression levels of sonic hedgehog pathway genes and their targets are upregulated in early clear cell renal cell carcinoma

et al. 2022

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Clear cell renal cell carcinoma (ccRCC) is the most common and aggressive subtype of kidney cancer, with high mortality rates worldwide. The sonic hedgehog (SHH) molecular cascade is altered in various malignancies in tumorigenesis, and several SHH pathway inhibitors have been considered as potential anticancer drugs. The aim of the present study was to determine the expression profile of SHH signaling components and their target genes in ccRCC. Additionally, the present study examined the effects of SHH pathway inhibitory drugs (RU-SKI43, cyclopamine and GLI-antagonist 61) on cell viability, cell cycle progression, expression levels of SHH target genes and migration ability in 786-O, ACHN and HK2 cells. The study also included paired tumor and normal samples from 62 patients with ccRCC. The mRNA levels in clinical samples and cell lines were measured via reverse transcription-quantitative PCR. Cell viability was examined using a sulforhodamine B assay. Flow cytometry was used to investigate cell cycle progression and the migratory rate of cells was assessed using a wound healing assay. High mRNA levels of SHH , smoothened ( SMO ), glioma-associated zinc finger protein ( GLI ) 1-3 , BCL2 apoptosis regulator ( BCL2 ), MYC proto-oncogene ( MYC ), vascular endothelial growth factor A ( VEGFA ) and cyclin D1 ( CCND1 ) were observed in the tumor tissues, especially in early ccRCC, according to the TNM stage or World Health Organization/International Society of Urological Pathology (ISUP) grade. High expression levels of VEGFA , as well as low CCND1 mRNA expression, were associated with short overall survival, and increased VEGFA expression was an independent prognostic factor of a poor outcome in patients with advanced ISUP grade (Cox hazard ratio test). Cyclopamine treatment was found to arrest 786-O cells in the G 2 /M phase and decreased the expression levels of GLI1 , BCL2 , VEGFA and CCND1 . RU-SKI43 inhibited cell migration and decreased the expression levels of BCL2 , MYC and CCND1 in ACHN cells. Overall, the results of the present study suggested that SHH signaling may be involved in the early development of ccRCC, and the expression levels of CCND1 and VEGFA may serve as prognostic factors of this disease. Cyclopamine and RU-SKI43 appear to be potential anti-renal cell carcinoma drugs; however, this hypothesis requires verification by further in vivo studies.

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Section: Discussionmentioning

confidence: 99%

Expression levels of sonic hedgehog pathway genes and their targets are upregulated in early clear cell renal cell carcinoma

et al. 2022

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“…Moreover, in breast cancer, Hh signaling has been shown to induce angiogenesis independently of VEGF activation [ 219 ]. Recently, a comprehensive immunohistochemistry (IHC) study by Kurebayashi et al showed that SHH expression was positively correlated with tumor size, Ki-67 labeling index, and HER2 positivity, but negatively correlated with estrogen receptor (ER+) and progesterone receptor (PR+) breast cancer [ 220 ]. In addition, a GLI1 isoform called truncated GLI1 (tGLI1) has also been reported to induce the activation of genes related to proliferation, migration, and angiogenesis of breast cancer.…”

Section: Hedgehog Signaling In Cancers and Its Inhibitorsmentioning

confidence: 99%

Hedgehog Signaling in Cancer: A Prospective Therapeutic Target for Eradicating Cancer Stem Cells

Sari

Phi

Jun

et al. 2018

Cells

149

103

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The Hedgehog (Hh) pathway is a signaling cascade that plays a crucial role in many fundamental processes, including embryonic development and tissue homeostasis. Moreover, emerging evidence has suggested that aberrant activation of Hh is associated with neoplastic transformations, malignant tumors, and drug resistance of a multitude of cancers. At the molecular level, it has been shown that Hh signaling drives the progression of cancers by regulating cancer cell proliferation, malignancy, metastasis, and the expansion of cancer stem cells (CSCs). Thus, a comprehensive understanding of Hh signaling during tumorigenesis and development of chemoresistance is necessary in order to identify potential therapeutic strategies to target various human cancers and their relapse. In this review, we discuss the molecular basis of the Hh signaling pathway and its abnormal activation in several types of human cancers. We also highlight the clinical development of Hh signaling inhibitors for cancer therapy as well as CSC-targeted therapy.

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“…HH signaling pathway has been reported to be involved in the pathogenesis of several types of female cancer, including breast [ 20 ], ovarian [ 21 ], endometrium [ 22 ], cervical [ 23 ], and uterine leiomyosarcoma [ 24 ] ( Figure 2 ).…”

Section: Hedgehog In Female Cancersmentioning

confidence: 99%

The Role of Hedgehog Pathway in Female Cancers

Garcia

Ulin

Al-Hendy

et al. 2020

J Cancer Sci Clin Ther

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Background: The hedgehog pathway (HH) is one of the key regulators involved in many biological events. Malfunction of this pathway is associated with a variety of diseases including several types of cancers. Methods: We collected data from public databases and conducted a comprehensive search linking the HH pathway with female cancers. In addition, we overviewed clinical trials of targeting HH pathway in female cancers. Results: The activation of HH pathway and its role in female cancers, including breast cancer, ovarian cancer, cervical cancer, endometrial cancer, and uterine leiomyosarcoma were summarized. Treatment options targeting SMO and GLI in HH pathway were reviewed and discussed. Conclusions: The hedgehog pathway was shown to be activated in several types of female cancers. Therefore, targeting HH pathway may be considered as a therapeutic option to be acknowledged in the treatment of female cancers.

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Comprehensive immunohistochemical analyses on expression levels of hedgehog signaling molecules in breast cancers

Abstract: This comprehensive analysis demonstrated for the first time that SHH, GLI1, and GLI2 expression levels positively correlated with the malignant phenotypes of tumor cells.

Cited by 10 publications

References 21 publications

Expression levels of sonic hedgehog pathway genes and their targets are upregulated in early clear cell renal cell carcinoma

Expression levels of sonic hedgehog pathway genes and their targets are upregulated in early clear cell renal cell carcinoma

Hedgehog Signaling in Cancer: A Prospective Therapeutic Target for Eradicating Cancer Stem Cells

The Role of Hedgehog Pathway in Female Cancers

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