We report a case of a 53-year-old woman with Grade 1 serous cystadenocarcinoma on her left ovary and metastatic serous adenocarcinoma on her right ovary. Serous carcinoma is the most common type of ovarian cancer, representing approximately half of all cases. Because of positive family history, the patient was referred for BRCA1/2 screening. Germline BRCA1 mutation c.676delT (p.C226VfsX8) was found, and in tumor tissue the normal allele was lost. Tumor tissue also had loss of heterozygosity in the PTCH1 gene, one of the major members of the Hedgehog-Gli (Hh-Gli) pathway. Gene expression analysis showed upregulation of the Hh-Gli pathway in both ovaries compared with healthy ovarian tissue. Primary cell culture was developed from the patient's tissue and showed downregulation of gene expression in response to cyclopamine, a Hh-Gli pathway inhibitor. The Hh-Gli signaling pathway may play a role in malignant transformation and metastasis of ovarian cancer.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1097/PGP.0b013e31823b6f0f | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Oncogenic potential of truncated-Gli3 via the Gsk3β/Gli3/AR-V7 axis in castration-resistant prostate cancer.
Oncogene
January 2025
Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, USA.
The functional activation of the androgen receptor (AR) and its interplay with the aberrant Hh/Gli cascade are pivotal in the progression of castration-resistant prostate cancer (CRPC) and resistance to AR-targeted therapies. Our study unveiled a novel role of the truncated form of Gli (t-Gli3) in advancing CRPC. Investigation into Gli3 regulation revealed a Smo-independent mechanism for its activation.
View Article and Find Full Text PDFGLI Transcriptional Targets S100A7 and KRT16 Show Upregulated Expression Patterns in Epidermis Overlying the Tumor Mass in Melanoma Samples.
Int J Mol Sci
May 2024
Division of Molecular Medicine, Ruđer Bošković Institute, Bijenička cesta 54, 10000 Zagreb, Croatia.
Although not completely understood, the role of the Hedgehog-GLI (HH-GLI) signaling pathway in melanoma and epithelial skin tumors has been reported before. In this study, we confirmed in various melanoma cell line models that keratin 16 (KRT16) and S100 Calcium-Binding Protein A7 (S100A7) are transcriptional targets of GLI Family Zinc Finger (GLI) proteins. Besides their important role in protecting and maintaining the epidermal barrier, keratins are somehow tightly connected with the S100 family of proteins.
View Article and Find Full Text PDFResveratrol nanoparticles induce apoptosis in oral cancer stem cells by disrupting the interaction between β-catenin and GLI-1 through p53-independent activation of p21.
Med Oncol
June 2024
Cancer Biology Division, School of Biotechnology, Kalinga Institute of Industrial Technology (KIIT), Deemed to be University, Campus-11, Patia, Bhubaneswar, 751024, Odisha, India.
Cancer stem cells (CSCs) are mainly responsible for tumorigenesis, chemoresistance, and cancer recurrence. CSCs growth and progression are regulated by multiple signaling cascades including Wnt/β-catenin and Hh/GLI-1, which acts independently or via crosstalk. Targeting the crosstalk of signaling pathways would be an effective approach to control the CSC population.
View Article and Find Full Text PDFTriptolide inhibits epithelial ovarian tumor growth by blocking the hedgehog/Gli pathway.
Aging (Albany NY)
October 2023
Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Nanchang University, Nanchang 330006, Jiangxi, P.R. China.
Epithelial ovarian cancer (EOC), the most predominant subtype of ovarian cancer (OC), involves poor prognosis and exhibits high aggression. Triptolide (TPL), like other Chinese herbs, has historically played a significant role in modern medicine. The screening system based on Gli-dependent luciferase reporter activity assessed the effects of over 800 natural medicinal materials on hedgehog (Hh) signaling pathway activity and discovered that TPL had an excellent inhibitory effect on Hh signaling pathway activity.
View Article and Find Full Text PDFTargeting cancer hallmark vulnerabilities in hematologic malignancies by interfering with Hedgehog/GLI signaling.
Blood
December 2023
Department of Biosciences and Medical Biology, Cancer Cluster Salzburg, Paris Lodron University of Salzburg, Salzburg, Austria.
Understanding the genetic alterations, disrupted signaling pathways, and hijacked mechanisms in oncogene-transformed hematologic cells is critical for the development of effective and durable treatment strategies against liquid tumors. In this review, we focus on the specific involvement of the Hedgehog (HH)/GLI pathway in the manifestation and initiation of various cancer features in hematologic malignancies, including multiple myeloma, T- and B-cell lymphomas, and lymphoid and myeloid leukemias. By reviewing canonical and noncanonical, Smoothened-independent HH/GLI signaling and summarizing preclinical in vitro and in vivo studies in hematologic malignancies, we elucidate common molecular mechanisms by which HH/GLI signaling controls key oncogenic processes and cancer hallmarks such as cell proliferation, cancer stem cell fate, genomic instability, microenvironment remodeling, and cell survival.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!