CDH1 and SNAI1 are regulated by E7 from human papillomavirus types 16 and 18

Rosendo‐Chalma, Pedro; Antonio-Véjar, Verónica; Bigoni‐Ordóñez, Gabriele Davide; Patiño‐Morales, Carlos César; Cano‐García, Amparo; García‐Carrancá, Alejandro

doi:10.3892/ijo.2020.5039

Cited by 6 publications

(10 citation statements)

References 70 publications

(96 reference statements)

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“…According to recent study of Rosendo-Chalma and collaborators, different from SiHa and Hela cell lines that showed mesenchymal-like phenotype, the Caski cells exhibit an epithelial phenotype which seems to reflect the impact of their distinct microenvironment. 33 The datasets using CSC-like derived from pharyngeal (GSE97510) and pancreatic (GSE36563) tumour cells did not present statistical differences when compared to adherent/monolayer cells.…”

Section: Discussionmentioning

confidence: 89%

A three‐dimensional microenvironment alters CD73 expression in cervical cancer

Iser

Mello

Davies

et al. 2021

Cell Biochemistry & Function

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Stem‐like cells (CSCs) have a tumour‐initiating capacity and play critical role in tumour metastasis, relapse and resistance to therapy. The ectoenzyme CD73, encoded by the NT5E gene, which catalyses the hydrolysis of AMP into adenosine, has been associated to an immunosuppressive tumour microenvironment, tumour cell adhesion and migration. Therefore, we investigated the expression and activity of CD73 in sphere‐forming cells from cervical cancer in comparison to monolayer cells in vitro. In addition, in silico analysis was performed to determine the expression of CD73 and other members of purinergic signalling in CSC‐like population derived from different tumour types in comparison to monolayer cells. CD73 protein expression levels and functionality in SiHa cells were analysed by flow cytometry and enzymatic assay, respectively. In silico investigation was performed through the analysis of seven datasets from different tumour types using GEO database. In vitro analysis showed a decreased CD73 protein expression and enzymatic activity in cervical spheres, when compared to monolayers. In addition, when sphere‐derived cells are re‐plated as monolayer culture, the CD73 expression and activity are restored. Supporting the in vitro results, in silico analysis showed that three‐dimensional spheres derived from cervical, thyroid and breast cancer presented decreased expression of CD73, when compared to their adherent counterparts. The decreased expression of CD73 in sphere‐derived cells or CSC‐enriched population reinforce its important role in cell adhesion, tumour spreading ability and metastasis, suggesting CD73 as potential target to be further investigated in cervical cancer.

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Section: Discussionmentioning

confidence: 89%

A three‐dimensional microenvironment alters CD73 expression in cervical cancer

Iser

Mello

Davies

et al. 2021

Cell Biochemistry & Function

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“…Nevertheless, we have observed that independent of the HPV genotype, cell lines derived from CC tumors can exhibit different CD73 expression levels and Ado generation capabilities 27 . Additionally, differences in cellular phenotypes have been reported, probably due to the microenvironment of origin; for instance, SiHa and HeLa cell lines show a mesenchymal‐like phenotype, while CaSki cells, which were obtained from omentum metastases, exhibit an epithelial phenotype 52 . In addition, CD73 function can differ in the same cell type from different tissues and within tumors, and the tumor cells themselves can differ in relation to CD73 expression compared to adjacent stromal cells.…”

Section: Discussionmentioning

confidence: 99%

“… 27 Additionally, differences in cellular phenotypes have been reported, probably due to the microenvironment of origin; for instance, SiHa and HeLa cell lines show a mesenchymal‐like phenotype, while CaSki cells, which were obtained from omentum metastases, exhibit an epithelial phenotype. 52 In addition, CD73 function can differ in the same cell type from different tissues and within tumors, and the tumor cells themselves can differ in relation to CD73 expression compared to adjacent stromal cells. The expression and activity of CD73 may also diverge depending on the stage of tumor development and different factors in the microenvironment leading to tumor progression.…”

Section: Discussionmentioning

confidence: 99%

Evidence that cervical cancer cells cultured as tumorspheres maintain high CD73 expression and increase their protumor characteristics through TGF‐β production

García‐Rocha¹,

García

Carrera‐Martínez

et al. 2022

Cell Biochemistry & Function

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Recently, a link between the biological activity of CD73 and tumorigenicity in solid tumors has been proposed. We previously reported that the generation of adenosine (Ado) by the activity of CD73 in cervical cancer (CC) cells induces transforming growth factor‐beta 1 (TGF‐β1) production to maintain CD73 expression. In the present study, we analyzed the participation of TGF‐β1 in CD73 expression and the development of protumoral characteristics in CaSki CC cells cultured as tumorspheres (CaSki‐T) and in monolayers (CaSki‐M). Compared with those in CaSki‐M cells, CD73 expression and Ado generation ability were significantly increased in CaSki‐T cells. CaSki‐T cells exhibited enrichment in the CSC‐like phenotype due to increases in the expression levels of stem cell markers (CD49f, CK17, and P63; OCT4 and SOX2), greater sphere formation efficiency (SFE), and an increase in the percentage of side population (SP) cells. Interestingly, compared with CaSki‐M cells, CaSki‐T cells produced a greater amount of TGF‐β1 and presented a marked protumor phenotype characterized by a significant decrease in the expression of major histocompatibility complex class‐I (MHC‐I) molecules, an increase in the expression of multidrug resistance protein‐I (MRP‐I) and vimentin, and an increase in the protein expression levels of Snail‐1 and Twist, which was strongly reversed with TGF‐β1 inhibition. These results suggest that the presence of TGF‐β1−CD73–Ado feedback loop can promote protumoral characteristics in the CC tumor microenvironment.

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“…In HPV‐induced cervical cancer, E‐cadherin expression is downregulated, while Snail and ZEB1 are markedly upregulated 183 . HR‐HPV E5/E7 is also implicated in this regulation 184,185 . Furthermore, HPV16/18 E7 curtails CDH1 and SNAI1 via DNA methylation 185 .…”

Section: Hpv and Its Pathogenesismentioning

confidence: 99%

Human papillomavirus associated cervical lesion: pathogenesis and therapeutic interventions

Ye,

Zheng,

et al. 2023

MedComm

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Human papillomavirus (HPV) is the most prevalent sexually transmitted virus globally. Persistent high‐risk HPV infection can result in cervical precancerous lesions and cervical cancer, with 70% of cervical cancer cases associated with high‐risk types HPV16 and 18. HPV infection imposes a significant financial and psychological burden. Therefore, studying methods to eradicate HPV infection and halt the progression of precancerous lesions remains crucial. This review comprehensively explores the mechanisms underlying HPV‐related cervical lesions, including the viral life cycle, immune factors, epithelial cell malignant transformation, and host and environmental contributing factors. Additionally, we provide a comprehensive overview of treatment methods for HPV‐related cervical precancerous lesions and cervical cancer. Our focus is on immunotherapy, encompassing HPV therapeutic vaccines, immune checkpoint inhibitors, and advanced adoptive T cell therapy. Furthermore, we summarize the commonly employed drugs and other nonsurgical treatments currently utilized in clinical practice for managing HPV infection and associated cervical lesions. Gene editing technology is currently undergoing clinical research and, although not yet employed officially in clinical treatment of cervical lesions, numerous preclinical studies have substantiated its efficacy. Therefore, it holds promise as a precise treatment strategy for HPV‐related cervical lesions.

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CDH1 and SNAI1 are regulated by E7 from human papillomavirus types 16 and 18

Cited by 6 publications

References 70 publications

A three‐dimensional microenvironment alters CD73 expression in cervical cancer

A three‐dimensional microenvironment alters CD73 expression in cervical cancer

Evidence that cervical cancer cells cultured as tumorspheres maintain high CD73 expression and increase their protumor characteristics through TGF‐β production

Human papillomavirus associated cervical lesion: pathogenesis and therapeutic interventions

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