Cross-talk between Human Papillomavirus Oncoproteins and Hedgehog Signaling Synergistically Promotes Stemness in Cervical Cancer Cells

Vishnoi, Kanchan; Mahata, Sutapa; Tyagi, Abhishek; Pandey, Arvind; Verma, G. S.; Jadli, Mohit; Singh, Tejveer; Singh, Sukh Mahendra; Bharti, Alok C.

doi:10.1038/srep34377

Cited by 37 publications

(35 citation statements)

References 42 publications

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“…Cervical cancer is one of the most common malignancies diagnosed in women [ 173 , 174 , 175 ]. Chronic infection with high-risk human papillomavirus and inherited polymorphism of cytokine genes are involved in cervical cancer emergence [ 176 , 177 , 178 , 179 , 180 ]. Hence, enhanced levels of cytokines participate in cervical cancer progression.…”

Section: Chrysin and Cancermentioning

confidence: 99%

Broad-Spectrum Preclinical Antitumor Activity of Chrysin: Current Trends and Future Perspectives

et al. 2020

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Pharmacological profile of phytochemicals has attracted much attention to their use in disease therapy. Since cancer is a major problem for public health with high mortality and morbidity worldwide, experiments have focused on revealing the anti-tumor activity of natural products. Flavonoids comprise a large family of natural products with different categories. Chrysin is a hydroxylated flavonoid belonging to the flavone category. Chrysin has demonstrated great potential in treating different disorders, due to possessing biological and therapeutic activities, such as antioxidant, anti-inflammatory, hepatoprotective, neuroprotective, etc. Over recent years, the anti-tumor activity of chrysin has been investigated, and in the present review, we provide a mechanistic discussion of the inhibitory effect of chrysin on proliferation and invasion of different cancer cells. Molecular pathways, such as Notch1, microRNAs, signal transducer and activator of transcription 3 (STAT3), nuclear factor-kappaB (NF-κB), PI3K/Akt, MAPK, etc., as targets of chrysin are discussed. The efficiency of chrysin in promoting anti-tumor activity of chemotherapeutic agents and suppressing drug resistance is described. Moreover, poor bioavailability, as one of the drawbacks of chrysin, is improved using various nanocarriers, such as micelles, polymeric nanoparticles, etc. This updated review will provide a direction for further studies in evaluating the anti-tumor activity of chrysin.

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Section: Chrysin and Cancermentioning

confidence: 99%

Broad-Spectrum Preclinical Antitumor Activity of Chrysin: Current Trends and Future Perspectives

et al. 2020

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“…Our findings, together with others, suggest that these “recurrent tumours” most likely constitute a new primary tumour that arises in a field of a molecularly altered epithelium. While the molecular pathways linked to disease recurrence are yet to be fully defined, the Hedgehog (Hh) pathway is of particular interest in this context, given that Hh pathway dysregulation has been described in cancers associated with highrisk human papillomavirus (HR-HPV) and chronic inflammation [ 6 , 7 ]; both of which are recognised independent aetiological factors for VSCC [ 4 ].…”

Section: Introductionmentioning

confidence: 99%

Under expression of the Sonic Hedgehog receptor, Patched1 (PTCH1), is associated with an increased risk of local recurrence in squamous cell carcinoma of the vulva arising on a background of Lichen Sclerosus

et al. 2018

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ObjectiveDysregulation of the Hedgehog (Hh) pathway has been described in a variety of cancers, including cervical cancer, a disease which shares a common aetiology with vulval squamous cell carcinoma (VSCC). Here, we investigate a large number of primary VSCC cases for evidence of Hedgehog pathway activation and examine the implications of pathway activity on clinical outcomes in a cohort of patients with primary VSCC.MethodsArchival histology blocks containing VSCC and histologically normal adjacent epithelium were retrieved from a cohort of 91 patients who underwent treatment for primary VSCC. Immunohistochemistry staining was undertaken to assess for the expression of key Hh pathway components (SHH, PTCH1, GLI1). A competing risks statistical model was used to evaluate the implications of the levels of key Hh pathway components on clinical outcomes.ResultsWe show that 92% of primary VSCC cases over-expressed one or more components of the Hh signalling pathway when compared to the adjacent normal epithelium. While expression of SHH and GLI1 did not correlate with any clinicopathological criteria, over- or under-expression of PTCH1 was associated with a reduced or increased risk of developing a local disease recurrence, respectively. In VSCC arising on a background of Lichen Sclerosus, the risk of local recurrence was potentiated in cases where PTCH1 was under-expressed.ConclusionsOur findings reveal, for the first time, that the Hh pathway is activated in VSCC and that PTCH1 expression can be used as a biomarker to stratify patients and inform clinicians of the risk of their local recurrence, particularly in cases of VSCC associated with LS.

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“…Constitutive expression of E6 and E7 is a necessary prerequisite for growth and survival of cervical cancer cells as well as initiation and maintenance of malignant transformation (47). Recent investigations from our group demonstrated novel role of HPVE6 in maintenance of stemness and chemoresistance in cervical cancer cells (50,51) by regulation of key signaling mediators like STAT3, Notch/hes and Gli (45,(50)(51)(52)(53). These leads make HPV oncoproteins and their upstream regulatory mechanism a suitable target to design effective anti-HPV therapeutics.…”

Section: Hpv Genome Of About 8 Kb Consists Of Eight Openmentioning

confidence: 99%

“…Efforts to develop siRNA-based anti-HPV therapeutics have been entirely focused around E6 and E7 transcripts of the high risk HPV16 and HPV18 (50,51,53, (Table 2). A superior silencing was observed if the E6 specific monoclonal antibodies were co-delivered with siRNA in intra-cytoplasmic compartment using liposomes (143).…”

Section: Silencing Hpv Rna By Rna Interferencementioning

confidence: 99%

Therapeutic startegies for human papillomavirus infection and associated cancers

et al. 2018

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Human papillomavirus (HPV) infection is linked to development of cancer of cervix, vagina, vulva, penis, ano-genital and non-genital oro-pharyngeal sites. HPV being a sexually transmitted virus infects both genders equally but with higher chances of pathological outcome in women. In the absence of organized screening programs, women report HPV-infected lesions at relatively advanced stages where they are subjected to standard treatments that are not HPV-specific. HPV infection-driven lesions usually take 10-20 years for malignant progression and are preceded by well-characterized pre-cancer stages. Despite availability of window for pharmacological intervention, therapeutic that could eradicate HPV from infected lesions is currently lacking. A variety of experimental approaches have been made to address this lacuna and there has been significant progress in a number of lead molecules which are in different stages of clinical and pre-clinical development. Present review provides a brief overview of the magnitude of the problem and current status of research on promising lead molecules, formulations and therapeutic strategies that showed potential to translate to clinically-viable HPV therapeutics to counteract this reproductive health challenge.

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Cross-talk between Human Papillomavirus Oncoproteins and Hedgehog Signaling Synergistically Promotes Stemness in Cervical Cancer Cells

Cited by 37 publications

References 42 publications

Broad-Spectrum Preclinical Antitumor Activity of Chrysin: Current Trends and Future Perspectives

Broad-Spectrum Preclinical Antitumor Activity of Chrysin: Current Trends and Future Perspectives

Under expression of the Sonic Hedgehog receptor, Patched1 (PTCH1), is associated with an increased risk of local recurrence in squamous cell carcinoma of the vulva arising on a background of Lichen Sclerosus

Therapeutic startegies for human papillomavirus infection and associated cancers

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