Wnt Signaling: A Potential Therapeutic Target in Head and Neck Squamous Cell Carcinoma

Javed, Zeeshan; Farooq, Hafiz Muhammad; Ullah, Mukhtar; Iqbal, Masood; Raza, Qamar; Sadia, Haleema; Pezzani, Raffaele; Salehi, Bahare; Sharifi‐Rad, Javad; Cho, William C.

doi:10.31557/apjcp.2019.20.4.995

Cited by 19 publications

(19 citation statements)

References 73 publications

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“…It is characteristic of the plane polarity signal that Rho-associated kinases can mediate cytoskeleton rearrangement. Alternatively, the PCP pathway can also be mediated by the triggering of RAC to initiate the c-Jun amino terminal kinase (JNK) signaling cascade (Javed et al, 2019). The activation of Dvl-mediated Wnt signal induces the activation of heterotrimeric G protein and promotes the transport of intracellular Ca 2+ to the extracellular environment (De, 2011).…”

Section: Non-canonical Wnt Signaling Pathwaymentioning

confidence: 99%

Roles of the Wnt Signaling Pathway in Head and Neck Squamous Cell Carcinoma

Xie

Huang

et al. 2021

Front. Mol. Biosci.

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Head and neck squamous cell carcinoma (HNSCC) is the most common type of head and neck tumor. It is a high incidence malignant tumor associated with a low survival rate and limited treatment options. Accumulating conclusions indicate that the Wnt signaling pathway plays a vital role in the pathobiological process of HNSCC. The canonical Wnt/β-catenin signaling pathway affects a variety of cellular progression, enabling tumor cells to maintain and further promote the immature stem-like phenotype, proliferate, prolong survival, and gain invasiveness. Genomic studies of head and neck tumors have shown that although β-catenin is not frequently mutated in HNSCC, its activity is not inhibited by mutations in upstream gene encoding β-catenin, NOTCH1, FAT1, and AJUBA. Genetic defects affect the components of the Wnt pathway in oral squamous cell carcinoma (OSCC) and the epigenetic mechanisms that regulate inhibitors of the Wnt pathway. This paper aims to summarize the groundbreaking discoveries and recent advances involving the Wnt signaling pathway and highlight the relevance of this pathway in head and neck squamous cell cancer, which will help provide new insights into improving the treatment of human HNSCC by interfering with the transcriptional signaling of Wnt.

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Section: Non-canonical Wnt Signaling Pathwaymentioning

confidence: 99%

Roles of the Wnt Signaling Pathway in Head and Neck Squamous Cell Carcinoma

Xie

Huang

et al. 2021

Front. Mol. Biosci.

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“…However, increasing evidence has shown that IFN-γ is a cytokine with both anticancer and carcinogenic functions (36,37). IFN-γ is generally regarded as an inflammatory cytokine and serves as an inducer of the activation of ERK and STAT3 signaling (38). Hence, in this paper, we used IFN-γ as an inducer of ERK1/2 and STAT3 phosphorylation.…”

Section: Discussionmentioning

confidence: 99%

Bupivacaine inhibits the malignant biological behavior of oral squamous cell carcinoma cells by inhibiting the activation of ERK1/2 and STAT3

Wang¹,

Zhang²,

Wen³

et al. 2021

Ann Transl Med

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Background: Oral squamous cell carcinoma (OSCC) is an aggressive malignant tumor. Bupivacaine (Bupi), a local anesthetic drug, has been shown to display anti-tumor activity against a variety of tumors. Methods: We selected OSCC CAL-27 cells as the in vitro model. Cell toxicity, proliferation, apoptosis, and stemness were conducted, respectively. The protein levels of Ki67, PCNA, caspase-3, caspase-9, survivin, SOX2, NANOG, OCT4, STAT3, p-STAT3, ERK1/2, and p-ERK1/2 were evaluated by western blotting.Male BALB/c nude mice xenograft model was used to evaluate the effect of Bupi on tumor growth in vivo. Results: Compared with the control group, Bupi (0.2, 0.5, or 1 μm) significantly decreased the cell viability and the proliferation of CAL-27 cells. Meanwhile, Bupi significantly promoted apoptosis of CAL-27 cells compared with the control group. Additionally, Bupi inhibited the stemness of CAL-27 cells which was evidenced by a sphere formation assay. Bupi decreased the phosphorylation level of STAT3 and ERK1/2 in a dose-dependent manner. The addition of interferon-γ (IFN-γ, 20 ng/mL) in the experiment verified the role of Bupi on STAT3 and ERK1/2 signaling. In vivo, Bupi (40 μmol/kg) obviously suppressed the weight and size of the xenograft tumor, the number of apoptotic cells and Ki67+ decreased. Also, Bupi treatment inhibited the expression of stem-like marker proteins.Conclusions: Bupi could be used as an anticancer drug against the growth and stemness ability of OSCC.The underlying mechanism may be due to down-regulation of STAT3 and ERK1/2 signaling. This study provides a new insight for the application of Bupi.

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“…Interestingly, despite Wnt/β-catenin's impact on head and neck cancers, there are very few reports of Wnt/β-catenin mutations associated with HNSCC. However, mutations in Wnt/β-catenin upstream regulators such as AJUBA can result in β-catenin stabilization [20,69] , which is correlated with dedifferentiation and poor prognosis [26,70] . As a scaffolding protein, AJUBA plays an essential role in oncogenesis by regulating major signaling pathways, such as Wnt, JAK/STAT, RAS/ERK, and Hippo.…”

Section: Discussionmentioning

confidence: 99%