3,426 results match your criteria activation hedgehog

Constitutive Hedgehog/GLI2 signaling drives extracutaneous basaloid squamous cell carcinoma development and bone remodeling.

Carcinogenesis 2021 Jun 12. Epub 2021 Jun 12.

Department of Dermatology, University of Michigan, Ann Arbor, MI, USA.

Uncontrolled activation of the Hedgehog (Hh) signaling pathway, operating through GLI transcription factors, plays a central role in the pathogenesis of cutaneous basal cell carcinoma and contributes to the development of several malignancies arising in extracutaneous sites. We now report that K5-tTA;tetO-Gli2 bitransgenic mice develop distinctive epithelial tumors within their jaws. These tumors consist of large masses of highly proliferative, monomorphous, basaloid cells with scattered foci of keratinization and central necrosis, mimicking human basaloid squamous cell carcinoma (BSCC), an aggressive upper aerodigestive tract tumor. Read More

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Resveratrol-mediated neurorestoration after cerebral ischemic injury - Sonic Hedgehog signaling pathway.

Life Sci 2021 Jun 8:119715. Epub 2021 Jun 8.

Department of Neurology, the First Affiliated Hospital of Chongqing Medical University, Chongqing, China. Electronic address:

Aims: Resveratrol pretreatment can decrease ischemic cerebral injury and enhance proliferation of neural stem cells via mediation of Sonic Hedgehog signaling. However, it is relatively little known about whether neurorestorative effects of resveratrol are mediated by Shh signaling in ischemic cerebral injury. The present study tests whether the Shh signaling pathway mediates resveratrol to promote neurorestoration of ischemic cerebral injury. Read More

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GLI1: A Therapeutic Target for Cancer.

Front Oncol 2021 25;11:673154. Epub 2021 May 25.

Oncology Department, Drug Discovery Division, Southern Research, Birmingham, AL, United States.

GLI1 is a transcriptional effector at the terminal end of the Hedgehog signaling (Hh) pathway and is tightly regulated during embryonic development and tissue patterning/differentiation. GLI1 has low-level expression in differentiated tissues, however, in certain cancers, aberrant activation of GLI1 has been linked to the promotion of numerous hallmarks of cancer, such as proliferation, survival, angiogenesis, metastasis, metabolic rewiring, and chemotherapeutic resistance. All of these are driven, in part, by GLI1's role in regulating cell cycle, DNA replication and DNA damage repair processes. Read More

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Adipocyte Fatty Acid Binding Protein Promotes the Onset and Progression of Liver Fibrosis via Mediating the Crosstalk between Liver Sinusoidal Endothelial Cells and Hepatic Stellate Cells.

Adv Sci (Weinh) 2021 06 27;8(11):e2003721. Epub 2021 Mar 27.

State Key Laboratory of Pharmaceutical Biotechnology, LKS Faculty of Medicine, the University of Hong Kong, Hong Kong, 999077, China.

Development of liver fibrosis results in drastic changes in the liver microenvironment, which in turn accelerates disease progression. Although the pathological function of various hepatic cells in fibrogenesis is identified, the crosstalk between them remains obscure. The present study demonstrates that hepatic expression of adipocyte fatty acid binding protein (A-FABP) is induced especially in the liver sinusoidal endothelial cells (LSECs) in mice after bile duct ligation (BDL). Read More

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Bone marrow mesenchymal stem cells and their derived exosomes resolve doxorubicin-induced chemobrain: critical role of their miRNA cargo.

Stem Cell Res Ther 2021 Jun 5;12(1):322. Epub 2021 Jun 5.

Department of Biochemistry, Faculty of Pharmacy, Ain Shams University, Cairo, 11566, Egypt.

Background: Doxorubicin (DOX), a widely used chemotherapeutic agent, can cause neurodegeneration in the brain, which leads to a condition known as chemobrain. In fact, chemobrain is a deteriorating condition which adversely affects the lives of cancer survivors. This study aimed to examine the potential therapeutic effects of bone marrow mesenchymal stem cells (BMSCs) and their derived exosomes (BMSCs-Exo) in DOX-induced chemobrain in rat models. Read More

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Silencing of Histone Deacetylase 6 Decreases Cellular Malignancy and Contributes to Primary Cilium Restoration, Epithelial-to-Mesenchymal Transition Reversion, and Autophagy Inhibition in Glioblastoma Cell Lines.

Biology (Basel) 2021 May 26;10(6). Epub 2021 May 26.

Department of Biochemistry and Genetics, University of Navarra School of Sciences, 31008 Pamplona, Spain.

Glioblastoma multiforme, the most common type of malignant brain tumor as well as the most aggressive one, lacks an effective therapy. Glioblastoma presents overexpression of mesenchymal markers Snail, Slug, and N-Cadherin and of the autophagic marker p62. Glioblastoma cell lines also present increased autophagy, overexpression of mesenchymal markers, Shh pathway activation, and lack of primary cilia. Read More

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Targeting Wnt Signaling in Endometrial Cancer.

Cancers (Basel) 2021 May 13;13(10). Epub 2021 May 13.

Stephenson Cancer Center, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA.

This review presents new findings on Wnt signaling in endometrial carcinoma and implications for possible future treatments. The Wnt proteins are essential mediators in cell signaling during vertebrate embryo development. Recent biochemical and genetic studies have provided significant insight into Wnt signaling, in particular in cell cycle regulation, inflammation, and cancer. Read More

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GAB1 overexpression identifies Hedgehog-activated anterior skull base meningiomas.

Neuropathol Appl Neurobiol 2021 May 31. Epub 2021 May 31.

CRICM INSERM U1127 CNRS UMR 7225, Institut du Cerveau et de la Moelle Epinière, Paris, F-75013, France.

Aims: Mutations activating the Hedgehog (Hh) signalling pathway have been described in anterior skull base meningiomas, raising hope for the use of targeted therapies. However, identification of Hh-activated tumours is hampered by the lack of a reliable immunohistochemical marker. We report the evaluation of GAB1, an immunohistochemical marker used to detect Hh pathway activation in medulloblastoma, as a potential marker of Hh-activated meningiomas. Read More

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Epigenetic regulation in medulloblastoma pathogenesis revealed by genetically engineered mouse models.

Cancer Sci 2021 May 29. Epub 2021 May 29.

Department of Biochemistry and Cellular Biology, National Center of Neurology and Psychiatry (NCNP), Tokyo, 187-8502, Japan.

Medulloblastoma is the most common malignant cerebellar tumor in children. Recent technological advances in multi-layered omics data analysis have revealed four molecular subgroups of medulloblastoma (Wingless/int, Sonic hedgehog, Group3 and Group4). (Epi)genomic and transcriptomic profiling on human primary medulloblastomas show distinct oncogenic drivers and cellular origin(s) across the subgroups. Read More

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Positive Crosstalk Between Hedgehog and NF-κB Pathways Is Dependent on KRAS Mutation in Pancreatic Ductal Adenocarcinoma.

Front Oncol 2021 11;11:652283. Epub 2021 May 11.

Department of Gastroenterology, Kunshan Affiliated Hospital of Nanjing University of Chinese Medicine, Suzhou, China.

It has been shown that aberrant activation of the Hedgehog (Hh) and nuclear factor-kappa B (NF-κB) signaling pathways plays an important role in the pancreatic carcinogenesis, and KRAS mutation is a hallmark of pancreatic ductal adenocarcinoma (PDAC). Until now, the role of KRAS mutation in the context of crosstalk between Hh and NF-κB signaling pathways in PDAC has not been investigated. This study was to determine whether the crosstalk between the Hh and NF-κB pathways is dependent on KRAS mutation in PDAC. Read More

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Hedgehog gene expression patterns among intrinsic subtypes of breast cancer: Prognostic relevance.

Pathol Res Pract 2021 May 13;223:153478. Epub 2021 May 13.

Research Unit, University General Hospital of Alicante, and Alicante Institute for Health and Biomedical Research (ISABIAL), Pintor Baeza 12, 03010 Alicante, Spain; Pathology Dept., University General Hospital of Alicante, and Alicante Institute for Health and Biomedical Research (ISABIAL), Pintor Baeza 12, 03010 Alicante, Spain.

Purpose: Hedgehog (Hh) signaling is a crucial developmental regulatory pathway recognized as a primary oncogenesis driver in various human cancers. However, its role in breast carcinoma (BC) has been underexplored.

Methods: We analyzed the expression of several Hh associated genes in a clinical series and breast cancer cell lines. Read More

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Hedgehog signaling modulates cigarette-induced COPD development.

Exp Ther Med 2021 Jul 4;22(1):729. Epub 2021 May 4.

Department of Respiratory and Critical Care Medicine, Shanghai Rui Jin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200025, P.R. China.

Hedgehog (Hh) signaling is involved in early embryogenesis and maintains quiescence in the adult lungs. The interruption of Hh signaling may lead to the development of chronic obstructive pulmonary disease (COPD). The current study aimed to assess whether the Hh pathway affects cigarette-induced emphysema and airway inflammation by regulating inflammatory cytokines. Read More

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Deterministic role of sonic hedgehog signalling pathway in specification of hemogenic versus endocardiogenic endothelium from differentiated human embryonic stem cells.

Cells Dev 2021 May 6;166:203685. Epub 2021 May 6.

Symbiosis Centre for Stem Cell Research (SCSCR), Symbiosis International University (SIU), Pune, India. Electronic address:

Embryonic stem cells (ESCs) have been shown to have an ability to form a large number of functional endothelial cells in vitro, but generating organ-specific endothelial cells remains a challenge. Sonic hedgehog (SHH) pathway is one of the crucial developmental pathways that control differentiation of many embryonic cell types such as neuroectodermal, primitive gut tube and developing limb buds; SHH pathway is important for functioning of adult cell of skin, bone, liver as well as it regulates haematopoiesis. Misregulation of SHH pathway leads to cancers such as hepatic, pancreatic, basal cell carcinoma, medulloblastoma, etc. Read More

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Co-culturing polarized M2 Thp-1-derived macrophages enhance stemness of lung adenocarcinoma A549 cells.

Ann Transl Med 2021 Apr;9(8):709

Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.

Background: The tumor microenvironment (TME) is highly associated with cancer stem cells, and affects tumor initiation, progression, and metastasis. This study aimed to explore the underlying molecular mechanism of induction of A549 cancer cell stemness by THP-1-derived macrophages.

Method: The Hedgehog inhibitor (Vismodegib), Notch inhibitor Gamma Secretase Inhibitor (GSI), and Signal Transducer and Activator of Transcription 3 (STAT3) inhibitor Cucurbitacin I (JSI-124) were added separately into the co-culture system of A549 cancer cell with THP-1-derived macrophages. Read More

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Interaction of tacrolimus through hedgehog signaling pathway: An in vitro evaluation using rat hepatocytes.

Hum Exp Toxicol 2021 May 12:9603271211017313. Epub 2021 May 12.

Cell and Molecular Biology Lab, Institute of Zoology, University of the Punjab, Lahore, Pakistan.

Tacrolimus (TAC) is the drug of choice in immunosuppressive therapy for organ transplantation; however, adverse effects are still a major concern. The current study aims to decipher the short-term exposure of TAC on rat hepatocytes in relation to activation of hedgehog (HH) signaling pathway. Time dependent study was conducted using primary rat hepatocytes treated with TAC (36 µM) for 6, 12, 24 and 48 h. Read More

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Mitochondria: A critical hub for hepatic stellate cells activation during chronic liver diseases: Mitochondria in hepatic stellate cells.

Hepatobiliary Pancreat Dis Int 2021 Apr 28. Epub 2021 Apr 28.

Department of Pharmacology, the Blue Lab, Molecular Medicine and Toxicology Division, Saveetha Dental College, Saveetha Institute of Medical and Technical Sciences (SIMATS), Chennai 600077, Tamil Nadu, India. Electronic address:

Background: Upon liver injury, quiescent hepatic stellate cells (qHSCs), reside in the perisinusoidal space, phenotypically transdifferentiate into myofibroblast-like cells (MFBs). The qHSCs in the normal liver are less fibrogenic, migratory, and also have less proliferative potential. However, activated HSCs (aHSCs) are more fibrogenic and have a high migratory and proliferative MFBs phenotype. Read More

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Wnt Signaling Cascades and Their Role in Coronary Artery Health and Disease.

J Cell Signal 2021 ;2(1):52-62

Section of Cardiovascular Medicine, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06510, USA.

The Wnt signaling is classified as two distinct pathways of canonical Wnt/β-catenin signaling, and the non-canonical pathways of planar cell polarity and Wnt/Ca pathways. However, the scientific discoveries in recent years have shown that canonical and non-canonical Wnts pathways are intertwined and have complex interaction with other major signaling pathways such as hedgehog, Hippo and TOR signaling. Wnt signaling plays important roles in cell proliferation, differentiation and migration during embryonic development. Read More

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January 2021

Identification of pseudolaric acid B as a novel Hedgehog pathway inhibitor in medulloblastoma.

Biochem Pharmacol 2021 May 6;190:114593. Epub 2021 May 6.

Institute of Clinical Pharmacology, Science and Technology Innovation Center, Guangzhou University of Chinese Medicine, Guangzhou 510405, China; Research Center of Chinese Herbal Resources Science and Engineering, School of Pharmaceutical Sciences; Key Laboratory of Chinese Medicinal Resource from Lingnan, Ministry of Education, Guangzhou University of Chinese Medicine, Guangzhou 510006, China. Electronic address:

Aberrant activation of the Hedgehog (Hh) pathway is implicated in the pathogenesis and development of multiple cancers, especially Hh-driven medulloblastoma (MB). Smoothened (SMO) is a promising therapeutic target of the Hh pathway in clinical cancer treatment. However, SMO mutations frequently occur, which leads to drug resistance and tumor relapse. Read More

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Targeting non-canonical activation of GLI1 by the SOX2-BRD4 transcriptional complex improves the efficacy of HEDGEHOG pathway inhibition in melanoma.

Oncogene 2021 Jun 6;40(22):3799-3814. Epub 2021 May 6.

Core Research Laboratory - Institute for Cancer Research and Prevention (ISPRO), Florence, Italy.

Despite the development of new targeted and immune therapies, the prognosis of metastatic melanoma remains bleak. Therefore, it is critical to better understand the mechanisms controlling advanced melanoma to develop more effective treatment regimens. Hedgehog/GLI (HH/GLI) signaling inhibitors targeting the central pathway transducer Smoothened (SMO) have shown to be clinical efficacious in skin cancer; however, several mechanisms of non-canonical HH/GLI pathway activation limit their efficacy. Read More

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Sonic hedgehog signaling is associated with resistance to zoledronic acid in CD133high/CD44high prostate cancer stem cells.

Mol Biol Rep 2021 Apr 4;48(4):3567-3578. Epub 2021 May 4.

Department of Histology and Embryology, Faculty of Medicine, Ege University, Izmir, 35080, Turkey.

Cancer stem cells (CSCs) are a unique population that has been linked to drug resistance and metastasis and recurrence of prostate cancer. The sonic hedgehog (SHH) signal regulates stem cells in normal prostate epithelium by affecting cell behavior, survival, proliferation, and maintenance. Aberrant SHH pathway activation leads to an unsuitable expansion of stem cell lineages in the prostate epithelium and the transformation of prostate CSCs (PCSCs). Read More

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LncRNA BLACAT1 Accelerates Non-small Cell Lung Cancer Through Up-Regulating the Activation of Sonic Hedgehog Pathway.

Front Oncol 2021 14;11:625253. Epub 2021 Apr 14.

Outpatient Department of External Injury and Wound, Huai'an Second People's Hospital and the Affiliated Huai'an Hospital of Xuzhou Medical University, Huai'an, China.

Recently, increasing evidence has displayed that lncRNAs can exhibit crucial function in cancer progression, including lung cancer. LncRNA bladder cancer-associated transcript 1 (BLACAT1) is reported to participate in various cancers. The aim of our current study was to investigate the function of BLACAT1 in non-small cell lung cancer progression and study the functional pathway. Read More

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Effectiveness, safety and utilization of vismodegib in locally advanced basal cell carcinoma under real-world conditions in Germany - The non-interventional study NIELS.

J Eur Acad Dermatol Venereol 2021 Apr 30. Epub 2021 Apr 30.

Klinik und Poliklinik für Dermatologie, Venerologie und Allergologie, Universitätsklinikum Essen, Essen, Germany.

Background: Basal cell carcinoma (BCC) can arise by the uncontrolled proliferation of cells from multiple epidermal compartments due to aberrant activation of the Hedgehog (Hh) signalling pathway. Vismodegib, a small-molecule inhibitor of this pathway, is approved for treatment of patients with locally advanced (la) BCC inappropriate for surgery or radiotherapy or patients with symptomatic metastatic (m) BCC.

Objectives: The aim of this non-interventional study was to assess effectiveness with a special focus on duration of response (DOR), safety and utilization of vismodegib for treatment of laBCC in daily practice in Germany. Read More

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Identification and characterization of primary cilia-positive salivary gland tumours exhibiting basaloid/myoepithelial differentiation.

J Pathol 2021 Apr 30. Epub 2021 Apr 30.

Department of Tumor Pathology, Hamamatsu University School of Medicine, Hamamatsu, Japan.

Primary cilia (PC) are non-motile, antenna-like structures on the cell surface. Many types of neoplasms exhibit PC loss, whereas in some neoplasms PC are retained and involved in tumourigenesis. To elucidate the PC status and characteristics of major salivary gland tumours (SGTs), we examined 100 major SGTs encompassing eight histopathological types by immunohistochemical analysis. Read More

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Blockade of TRPM7 Alleviates Chondrocyte Apoptosis and Articular Cartilage Damage in the Adjuvant Arthritis Rat Model Through Regulation of the Indian Hedgehog Signaling Pathway.

Front Pharmacol 2021 13;12:655551. Epub 2021 Apr 13.

Department of Clinical Pharmacology, The Second Hospital of Anhui Medical University, Hefei, China.

Articular cartilage damage with subsequent impairment of joint function is a common feature of articular diseases, in particular, rheumatoid arthritis and osteoarthritis. While articular cartilage injury mediated by chondrocyte apoptosis is a known major pathological feature of arthritis, the specific mechanisms remain unclear at present. Transient receptor potential melastatin-like seven channel (TRPM7) is reported to play an important regulatory role in apoptosis. Read More

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Silencing of CD147 inhibits hepatic stellate cells activation related to suppressing aerobic glycolysis via hedgehog signaling.

Cytotechnology 2021 Apr 18;73(2):233-242. Epub 2021 Feb 18.

Department of Laboratory Medicine, The First Affiliated Hospital of Xi'an Medical University, Xi'an, 710077 Shaanxi China.

Hepatic stellate cells (HSCs) activation is a key step that promotes hepatic fibrosis. Emerging evidence suggests that aerobic glycolysis is one of its important metabolic characteristics. Our previous study has reported that CD147, a glycosylated transmembrane protein, contributes significantly to the activation of HSCs. Read More

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Estrogen withdrawal alters cytoskeletal and primary ciliary dynamics resulting in increased Hedgehog and osteoclastogenic paracrine signalling in osteocytes.

Sci Rep 2021 Apr 29;11(1):9272. Epub 2021 Apr 29.

Centre for Research in Medical Devices (CÚRAM), National University of Ireland, Galway, Ireland.

Estrogen deficiency during post-menopausal osteoporosis leads to osteoclastogenesis and bone loss. Increased pro-osteoclastogenic signalling (RANKL/OPG) by osteocytes occurs following estrogen withdrawal (EW) and is associated with impaired focal adhesions (FAs) and a disrupted actin cytoskeleton. RANKL production is mediated by Hedgehog signalling in osteocytes, a signalling pathway associated with the primary cilium, and the ciliary structure is tightly coupled to the cytoskeleton. Read More

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Role of SHH in Patterning Human Pluripotent Cells towards Ventral Forebrain Fates.

Cells 2021 Apr 16;10(4). Epub 2021 Apr 16.

Child Study Center, Yale University, New Haven, CT 06520, USA.

The complexities of human neurodevelopment have historically been challenging to decipher but continue to be of great interest in the contexts of healthy neurobiology and disease. The classic animal models and monolayer in vitro systems have limited the types of questions scientists can strive to answer in addition to the technical ability to answer them. However, the tridimensional human stem cell-derived organoid system provides the unique opportunity to model human development and mimic the diverse cellular composition of human organs. Read More

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Activation of Cilia-Independent Hedgehog/GLI1 Signaling as a Novel Concept for Neuroblastoma Therapy.

Cancers (Basel) 2021 Apr 15;13(8). Epub 2021 Apr 15.

Center for Tumor- and Immune Biology, Department of Gastroenterology, Philipps University Marburg, 35043 Marburg, Germany.

Although being rare in absolute numbers, neuroblastoma (NB) represents the most frequent solid tumor in infants and young children. Therapy options and prognosis are comparably good for NB patients except for the high risk stage 4 class. Particularly in adolescent patients with certain genetic alterations, 5-year survival rates can drop below 30%, necessitating the development of novel therapy approaches. Read More

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Steroidal alkaloids isolated from Veratrum grandiflorum Loes. as novel Smoothened inhibitors with anti-proliferation effects on DAOY medulloblastoma cells.

Bioorg Med Chem 2021 Jun 21;39:116166. Epub 2021 Apr 21.

Key Laboratory of Neuropsychiatric Drug Research of Zhejiang Province, Institute of Materia Medica, Hangzhou Medical College, Hangzhou, Zhejiang 310013, China. Electronic address:

Constitutive activation of Hedgehog (Hh) pathway is intimately related with the occurrence and development of several malignancies, such as medulloblastoma (MB) and other tumors. Therefore, small molecular inhibitors of Hh pathway are urgently needed. In this study, three new steroidal alkaloids, ⊿ (20R, 24R) 23-oxo-24-methylsolacongetidine, ⊿ (20S, 24R) 23-oxo-24-methylsolacongetidine and veralinine 3-O-α-l-rhamnopyranosyl-(1 → 2)-β-D-glucopyranoside, together with six known alkaloids, 20-epi-verazine, verazine, protoverine 15-(l)-2'-methylbutyrate, jervine, veramarine and β1-chaconine, were isolated and determined from Veratrum grandiflorum Loes. Read More

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Sonic Hedgehog signaling pathway in gynecological and genitourinary cancer (Review).

Int J Mol Med 2021 Jun 28;47(6). Epub 2021 Apr 28.

Department of Histology, Faculty of Medicine, Medical University of Gdansk, 80211 Gdansk, Poland.

Cancers of the urinary tract, as well as those of the female and male reproductive systems, account for a large percentage of malignancies worldwide. Mortality is frequently affected by late diagnosis or therapeutic difficulties. The Sonic Hedgehog (SHH) pathway is an evolutionary conserved molecular cascade, which is mainly associated with the development of the central nervous system in fetal life. Read More

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