Sonic Hedgehog Signalling Pathway and Ameloblastoma – A Review

Mishra, Pallavi; Panda, Anita; Bandyopadhyay, Anjan; Kumar, Harsh; Mohiddin, Gouse

doi:10.7860/jcdr/2015/15443.6750

Cited by 23 publications

(27 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…To further strengthen the association of MAPK signaling with ameloblastoma, the mutations in the RAS gene that acts upstream of BRAF and fibroblast growth factor receptor 2 (FGFR2), a membrane‐bound activator of MAPK signaling, have also been identified in ameloblastomas (Brown et al , ; Sweeney et al , ). Additionally, mutations in non‐MAPK signaling genes especially smoothened (SMO), a G protein‐coupled receptor and signaling effector component of the S HH signaling pathway, have also been described in ameloblastoma (Mishra et al , ). Taken together, these more recent molecular data strongly indicate the existence of unique genetic abnormalities that eventually lead to development of ameloblastoma (Sweeney et al , ; Brown and Betz, ; Brown et al , ).…”

Section: Advances In Etiopathogenesis Of Ameloblastomamentioning

confidence: 99%

“…Similarly, targeted therapies have been developed to control the effect of SMO mutation associated with pathogenesis of ameloblastoma (Mishra et al , ). These include vismodegib and itraconazole, which unfortunately have been less successful in controlling ameloblastoma associated with SMO mutations W535L and L412F due to resistance mechanisms that block binding of SMO‐targeted drugs (Sweeney et al , ).…”

Section: Current Management Approaches In Ameloblastomamentioning

confidence: 99%

“…On the contrary, arsenic trioxide and KAAD‐cyclopamine are known to be highly effective against these same mutations and may be useful in the treatment of ameloblastoma associated with SHH signaling pathway (Sweeney et al , ). As SHH expression is high in ameloblastomas, several drugs already developed to antagonize SHH signaling offer other non‐surgical targeted therapeutic options for ameloblastoma patients (Mishra et al , ). Among these, cyclopamine is the most widely used, but its main drawback is the inhibition of osteoblastic proliferation and differentiation that are important for bone healing (Stanton and Peng, ; Schaefer et al , ).…”

Section: Current Management Approaches In Ameloblastomamentioning

confidence: 99%

See 2 more Smart Citations

Ameloblastoma: current etiopathological concepts and management

et al. 2017

View full text Add to dashboard Cite

Ameloblastoma is a benign odontogenic tumor of epithelial origin. It is locally aggressive with unlimited growth capacity and has a high potential for malignant transformation as well as metastasis. Ameloblastoma has no established preventive measures although majority of patients are between ages 30 and 60 years. Molecular and genetic factors that promote oncogenic transformation of odontogenic epithelium to ameloblastoma are strongly linked to dysregulation of multiple genes associated with mitogen-activated protein kinase, sonic hedgehog, and WNT/b-catenin signaling pathways. Treatment of ameloblastoma is focused on surgical resection with a wide margin of normal tissue because of its high propensity for locoregional invasion; but this is often associated with significant patient morbidity. The relatively high recurrence rate of ameloblastoma is influenced by the type of molecular etiological factors, the management approach, and how early the patient presents for treatment. It is expected that further elucidation of molecular factors that orchestrate pathogenesis and recurrence of ameloblastoma will lead to new diagnostic markers and targeted drug therapies for ameloblastoma. Oral Diseases (2018) 24, 307-316

show abstract

Section: Advances In Etiopathogenesis Of Ameloblastomamentioning

confidence: 99%

Section: Current Management Approaches In Ameloblastomamentioning

confidence: 99%

Section: Current Management Approaches In Ameloblastomamentioning

confidence: 99%

See 1 more Smart Citation

Ameloblastoma: current etiopathological concepts and management

et al. 2017

View full text Add to dashboard Cite

show abstract

“…Therefore, radical surgical treatment is usually recommended for AMs, but usually results in morbid defects involving bone, teeth, and orofacial soft tissues . Although several hypotheses, including mutation of certain genes such as BRAFV600E , smoothened, and adenomatosis polyposis coli gene , the exact etiology of AM remains unclear. Further delineating the cellular and molecular mechanisms underlying the pathophysiology of AM may lead to the development of novel, non‐invasive, and targeted therapeutic modalities for this benign yet aggressive tumor.…”

Section: Introductionmentioning

confidence: 99%

Mesenchymal Stromal Cell-Derived Interleukin-6 Promotes Epithelial–Mesenchymal Transition and Acquisition of Epithelial Stem-Like Cell Properties in Ameloblastoma Epithelial Cells

et al. 2017

View full text Add to dashboard Cite

Epithelial-mesenchymal transition (EMT), a biological process associated with cancer stem-like or cancer-initiating cell formation, contributes to the invasiveness, metastasis, drug resistance, and recurrence of the malignant tumors; it remains to be determined whether similar processes contribute to the pathogenesis and progression of ameloblastoma (AM), a benign but locally invasive odontogenic neoplasm. Here, we demonstrated that EMT- and stem cell-related genes were expressed in the epithelial islands of the most common histologic variant subtype, the follicular AM. Our results revealed elevated interleukin (IL)-6 signals that were differentially expressed in the stromal compartment of the follicular AM. To explore the stromal effect on tumor pathogenesis, we isolated and characterized both mesenchymal stromal cells (AM-MSCs) and epithelial cells (AM-EpiCs) from follicular AM and demonstrated that, in in vitro culture, AM-MSCs secreted a significantly higher level of IL-6 as compared to the counterpart AM-EpiCs. Furthermore, both in vitro and in vivo studies revealed that exogenous and AM-MSC-derived IL-6 induced the expression of EMT- and stem cell-related genes in AM-EpiCs, whereas such effects were significantly abrogated either by a specific inhibitor of STAT3 or ERK1/2, or by knockdown of Slug gene expression. These findings suggest that AM-MSC-derived IL-6 promotes tumor-stem like cell formation by inducing EMT process in AM-EpiCs through STAT3 and ERK1/2-mediated signaling pathways, implying a role in the etiology and progression of the benign but locally invasive neoplasm. Stem Cells 2017;35:2083-2094.

show abstract

“…Aberrant expression of SHH is implicated in the development of several tumors, including brain, pancreas, and BC [12][13][14]. Glioma-Associated Oncogene Family Zinc Finger 1 (Gli-1) is a transcriptional factor of the Hedgehog pathway [15][16][17]. Recent study has shown that the expression of Gli-1 is higher in TNBC cell lines and promotes angiogenesis by transcriptional modulation of the VEGFR2 [18].…”

Section: Introductionmentioning

confidence: 99%

LOC101930370/MiR-1471 Axis Modulates the Hedgehog Signaling Pathway in Breast Cancer

Liu

Zhao

Bai

et al. 2018

Cell Physiol Biochem

View full text Add to dashboard Cite

Background/Aims: Non-coding RNAs (ncRNAs) play vital regulatory roles in many tumors. However, the functional roles of these transcripts responsible for their dysregulation in breast cancer (BC) are not thoroughly understood. Methods: We examined the expression of microRNA miR-1471 in BC specimens. Online analysis tools predicted that lncRNA LOC101930370 might act as an endogenous ‘sponge’ by competing for miR-1471 binding targets. Luciferase assays were used to prove the interaction of LOC101930370, miR-1471 and SHH. Edu, wound-healing and transwell assays were used to verify the contribution of miR-1471 and LOC101930370 on MCF-7 cells proliferation and metastasis. Gain and loss of function studies were performed to evaluate the relevance of Hedgehog pathway with LOC101930370/miR-1471 regulating axis in MCF-7 cells. Results: The expression of miR-1471 was markedly downregulated in BC. Inhibition of miR-1471 by LOC101930370 was proved by luciferase assay. Knockdown of LOC101930370 suppressed BC cells progression. MiR-1471 inhibitor resulted in a more aggressive metastasis of MCF-7 cells. Moreover, SHH and Gli-1 expression were significantly suppressed by LOC101930370 knockdown, and upregulated by miR-1471 inhibitor transfection. Conclusions: Collectively, our study reveals the interaction between LOC101930370 and miR-1471 for the first time. LOC101930370 positively regulates the expression of SHH by sponging miR-1471, which sheds new light on lncRNA-directed diagnostics and therapeutics in BC.

show abstract

Sonic Hedgehog Signalling Pathway and Ameloblastoma – A Review

Cited by 23 publications

References 33 publications

Ameloblastoma: current etiopathological concepts and management

Ameloblastoma: current etiopathological concepts and management

Mesenchymal Stromal Cell-Derived Interleukin-6 Promotes Epithelial–Mesenchymal Transition and Acquisition of Epithelial Stem-Like Cell Properties in Ameloblastoma Epithelial Cells

LOC101930370/MiR-1471 Axis Modulates the Hedgehog Signaling Pathway in Breast Cancer

Contact Info

Product

Resources

About