The role of Hedgehog and Notch signaling pathway in cancer

Xia, Rong; Xu, Maosen; Yang, Jing; Ma, Xuelei

doi:10.1186/s43556-022-00099-8

Cited by 13 publications

(11 citation statements)

References 464 publications

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“…In addition, we observed a relation between CAXII and the Hh pathway, as CAXII expression was modulated by cyclopamine (SMO antagonist) and SMO agonist (SAG). Indeed, the Hh pathway interacts with many others signalling pathways, such as Notch and Wnt; this crosstalk causes a synergistic effect observed in tumorigenesis [ 26 ].…”

Section: Discussionmentioning

confidence: 99%

Hedgehog Pathway Inhibition by Novel Small Molecules Impairs Melanoma Cell Migration and Invasion under Hypoxia

Falsini,

Giuntini,

Mori

et al. 2024

Pharmaceuticals

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Melanoma is the principal cause of death in skin cancer due to its ability to invade and cause metastasis. Hypoxia, which characterises the tumour microenvironment (TME), plays an important role in melanoma development, as cancer cells can adapt and acquire a more aggressive phenotype. Carbonic anhydrases (CA) activity, involved in pH regulation, is related to melanoma cell migration and invasion. Furthermore, the Hedgehog (Hh) pathway, already known for its role in physiological processes, is a pivotal character in cancer cell growth and can represent a promising pharmacological target. In this study, we targeted Hh pathway components with cyclopamine, glabrescione B and C22 in order to observe their effect on carbonic anhydrase XII (CAXII) expression especially under hypoxia. We then performed a migration and invasion assay on two melanoma cell lines (SK-MEL-28 and A375) where Smoothened, the upstream protein involved in Hh regulation, and GLI1, the main transcription factor that determines Hh pathway activation, were chemically inhibited. Data suggest the existence of a relationship between CAXII, hypoxia and the Hedgehog pathway demonstrating that the chemical inhibition of the Hh pathway and CAXII reduction resulted in melanoma migration and invasion impairment especially under hypoxia. As in recent years drug resistance to small molecules has arisen, the development of new chemical compounds is crucial. The multitarget Hh inhibitor C22 proved to be effective without signs of cytotoxicity and, for this reason, it can represent a promising compound for future studies, with the aim to reach a better melanoma disease management.

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Section: Discussionmentioning

confidence: 99%

Hedgehog Pathway Inhibition by Novel Small Molecules Impairs Melanoma Cell Migration and Invasion under Hypoxia

Falsini,

Giuntini,

Mori

et al. 2024

Pharmaceuticals

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“…Hh signaling engagement participates in facilitating growth and treatment resistance across a wide variety of cancers [102][103][104][105][106][107]. This is also the case in rhabdomyosarcoma [88,[108][109][110][111][112][113].…”

Section: Itraconazole and Hhmentioning

confidence: 97%

SALIQ in Rhabdomyosarcoma: A Repurposed Multidrug Regimen to Augment Standard Treatments by Adding Simvastatin, All Trans Retinoic Acid, Lithium, Itraconazole, and Quercetin

Kast,

Zaghloul,

Sardi

et al. 2023

Preprint

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Rhabdomyosarcoma is a cancer arising from arrested myogenic differentiation, seen mainly in children or adolescents. Metastatic rhabdomyosarcoma is often fatal even with aggressive cytotoxic chemotherapies, surgery, and irradiation. SALIQ is an acronym for a multidrug augmentation regimen designed as an adjunct to current rhabdomyosarcoma chemotherapies. SALIQ uses five common non-oncology drugs, repurposed from general medicine use, to promote malignant clone maturation and inhibit rhabdomyosarcoma growth. The five drugs are: the cholesterol lowering drug simvastatin, the acne medicine tretinoin (ATRA), the psychiatric drug lithium carbonate, the antifungal drug itraconazole, and the food supplement quercetin. All five drugs are in common use for non-cancer conditions, are cheap, have an eminently safe side effect profile, and all five have preclinical evidence and good rationale for inhibiting rhabdomyosarcoma growth.

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“…Hh induction of TGF-β-1 signaling has been correlated with increased motility and invasiveness in gastric cancer [ 90 ]. Hh enhancement of JAG2 expression has been shown to augment the Notch pathway [ 91 ]. Furthermore, the inhibition of Hh signaling in pancreatic cancer cells has demonstrated the impairment of EMT-mediated disease progression [ 92 ].…”

Section: Epithelial-to-mesenchymal Transition In Cancer Progressionmentioning

confidence: 99%

Epithelial-to-Mesenchymal Transition-Related Markers in Prostate Cancer: From Bench to Bedside

Gogola

Rejzer

Bahmad

et al. 2023

Cancers

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Prostate cancer (PCa) is the second most frequent type of cancer in men worldwide, with 288,300 new cases and 34,700 deaths estimated in the United States in 2023. Treatment options for early-stage disease include external beam radiation therapy, brachytherapy, radical prostatectomy, active surveillance, or a combination of these. In advanced cases, androgen-deprivation therapy (ADT) is considered the first-line therapy; however, PCa in most patients eventually progresses to castration-resistant prostate cancer (CRPC) despite ADT. Nonetheless, the transition from androgen-dependent to androgen-independent tumors is not yet fully understood. The physiological processes of epithelial-to-non-epithelial (“mesenchymal”) transition (EMT) and mesenchymal-to-epithelial transition (MET) are essential for normal embryonic development; however, they have also been linked to higher tumor grade, metastatic progression, and treatment resistance. Due to this association, EMT and MET have been identified as important targets for novel cancer therapies, including CRPC. Here, we discuss the transcriptional factors and signaling pathways involved in EMT, in addition to the diagnostic and prognostic biomarkers that have been identified in these processes. We also tackle the various studies that have been conducted from bench to bedside and the current landscape of EMT-targeted therapies.

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The role of Hedgehog and Notch signaling pathway in cancer

Cited by 13 publications

References 464 publications

Hedgehog Pathway Inhibition by Novel Small Molecules Impairs Melanoma Cell Migration and Invasion under Hypoxia

Hedgehog Pathway Inhibition by Novel Small Molecules Impairs Melanoma Cell Migration and Invasion under Hypoxia

SALIQ in Rhabdomyosarcoma: A Repurposed Multidrug Regimen to Augment Standard Treatments by Adding Simvastatin, All Trans Retinoic Acid, Lithium, Itraconazole, and Quercetin

Epithelial-to-Mesenchymal Transition-Related Markers in Prostate Cancer: From Bench to Bedside

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