CD71+ Population Enriched by HPV-E6 Protein Promotes Cancer Aggressiveness and Radioresistance in Cervical Cancer Cells

Leung, Thomas; Tang, Hermit Wai-Man; Siu, Michelle K.Y.; Chan, David; Chan, Ki; Cheung, Annie Nga‐Yin; Ngan, Hextan Y.S.

doi:10.1158/1541-7786.mcr-19-0068

Cited by 16 publications

(12 citation statements)

References 32 publications

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“…HPV16 E6 and E7 reduced G0/G1 cell cycle arrest, promoted a cancer stem-like phenotype and an anti-apoptotic effect, enhanced migration, invasion, spherogenesis, and increased chemoresistance and radioresistance after ionizing radiation in esophageal squamous cell carcinoma ( 210 ). A subpopulation of HPV-E6 positive cervical cancer cells enriched with CD71, a glycoprotein detected with poorly differentiated acute myeloid leukemia ( 216 ) and radioresistant glioma cells with cancer stem-like cells properties ( 217 ), demonstrated resistance to irradiation, an enhanced self-renewal ability, proliferation and tumorigenicity ( 211 ), in addition to higher transcriptional levels of some genes related to stemness including OCT-4, Nanog, ABCG2, and Bmi-1 ( 212 ). Furthermore, HPV16 E6 was shown to be actively involved in migration and invasion potentials, with elevated levels of functional and molecular markers of epithelial-to-mesenchymal transition (EMT) such as Snail, Slug, Twist, and vimentin, which could promote chemoresistance in cervical cancer ( 213 ).…”

Section: Introductionmentioning

confidence: 99%

Polyploid Giant Cancer Cells, a Hallmark of Oncoviruses and a New Therapeutic Challenge

Herbein

Nehme

2020

Front. Oncol.

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Tumors are renowned as intricate systems that harbor heterogeneous cancer cells with distinctly diverse molecular signatures, sizes and genomic contents. Among those various genomic clonal populations within the complex tumoral architecture are the polyploid giant cancer cells (PGCC). Although described for over a century, PGCC are increasingly being recognized for their prominent role in tumorigenesis, metastasis, therapy resistance and tumor repopulation after therapy. A shared characteristic among all tumors triggered by oncoviruses is the presence of polyploidy. Those include Human Papillomaviruses (HPV), Epstein Barr Virus (EBV), Hepatitis B and C viruses (HBV and HCV, respectively), Human T-cell lymphotropic virus-1 (HTLV-1), Kaposi's sarcoma herpesvirus (KSHV) and Merkel polyomavirus (MCPyV). Distinct viral proteins, for instance Tax for HTLV-1 or HBx for HBV have demonstrated their etiologic role in favoring the appearance of PGCC. Different intriguing biological mechanisms employed by oncogenic viruses, in addition to viruses with high oncogenic potential such as human cytomegalovirus, could support the generation of PGCC, including induction of endoreplication, inactivation of tumor suppressors, development of hypoxia, activation of cellular senescence and others. Interestingly, chemoresistance and radioresistance have been reported in the context of oncovirus-induced cancers, for example KSHV and EBV-associated lymphomas and high-risk HPV-related cervical cancer. This points toward a potential linkage between the previously mentioned players and highlights PGCC as keystone cancer cells in virally-induced tumors. Subsequently, although new therapeutic approaches are actively needed to fight PGCC, attention should also be drawn to reveal the relationship between PGCC and oncoviruses, with the ultimate goal of establishing effective therapeutic platforms for treatment of virus-associated cancers. This review discusses the presence of PGCCs in tumors induced by oncoviruses, biological mechanisms potentially favoring their appearance, as well as their consequent implication at the clinical and therapeutic level.

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Section: Introductionmentioning

confidence: 99%

Polyploid Giant Cancer Cells, a Hallmark of Oncoviruses and a New Therapeutic Challenge

Herbein

Nehme

2020

Front. Oncol.

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“…The identification of cell surface markers in cancer can establish differentiation to target specific sites. Some research confirmed a novel affiliation between HPV-E6 oncoprotein expression and the increase in the CD55 and CD71 floor markers in most cervical cancer cells ( 60 , 61 ). The HPV-E6 oncoprotein enriched the CD55 and CD71 populations, which increased cell proliferation, cell self-renewal ability, cell migration, radioresistance, and tumorigenicity.…”

Section: Application Of Crispr-cas9 In Hpv Cancer Therapymentioning

confidence: 83%

Description of CRISPR-Cas9 development and its prospects in human papillomavirus-driven cancer treatment

Wei

Zhang

2022

Front. Immunol.

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Human papillomaviruses (HPVs) have been recognized as the etiologic agents of various cancers and are called HPV-driven cancers. Concerning HPV-mediated carcinogenic action, gene therapy can cure cancer at the molecular level by means of the correction of specific genes or sites. CRISPR-Cas9, as a novel genetic editing technique, can correct errors in the genome and change the gene expression and function in cells efficiently, quickly, and with relative ease. Herein, we overviewed studies of CRISPR-mediated gene remedies for HPV-driven cancers and summarized the potential applications of CRISPR-Cas9 in gene therapy for cancer.

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“…The pathogenic mechanism of HPV is mainly through the viral oncoproteins E6 and E7, where E6 protein binds to the host pro‐apoptotic tumor suppressor, p53, and E7 binds to the retinoblastoma tumor suppressor protein, retinoblastoma protein (pRb), eventually causing cell proliferation, deformation, and canceration . As CRISPR‐Cas9 can efficiently cut and knock out pathogenic genes, it brings new hope for cervical cancer treatment, and it has in recent years made great progress in cervical cancer treatment (summarized in Table ).…”

Section: Cervical Cancer and Crispr‐cas9mentioning

confidence: 99%

Applications of CRISPR‐Cas9 in gynecological cancer research

et al. 2020

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Gynecological cancers pose a significant threat to women's health worldwide, with cervical cancer, ovarian cancer, and endometrial cancer having high incidences.Current gynecological cancer treatment methods mainly include surgery, chemotherapy, radiotherapy, and chemoradiotherapy. The CRISPR-Cas9 gene editing technology as a new therapeutic method has shown tremendous effect in the treatment of other cancers, promoting research on its potential therapeutic effect in gynecological cancer. In this article, we reviewed the current research status of CRISPR-Cas9 technology in gynecological cancer, focusing on the importance of studying the mechanism of CRISPR-Cas9 in gynecological cancer treatment, thereby laying a foundation for further research on its clinical application. K E Y W O R D S cancer treatment, CRISPR-Cas9, gene editing, gynecological cancers 1 | INTRODUCTIONThe CRISPR sequence, a cluster of regularly spaced short palindromic repeats, is a special ordered repeating sequence found in the genome of Escherichia coli. The CRISPR-Cas9 system constitutes the acquired immune system of E. coli. 1 In 2012, scientists discovered that the CRISPR-Cas9 system can produce mature CRISPR RNA (crRNA) and trans-activating crRNA (tracrRNA), which form a composite structure and have a directional guidance function to guide Cas9 to specific DNA sequences, resulting in DNA double-strand breaks. 2 By 2013, scientists had successfully edited the genome of eukaryotic cells using the CRISPR-Cas9 system. [3][4][5] Since then, the CRISPR-Cas9 gene editing technology has dramatically impacted the field of life sciences and has become one of the most significant research areas at present. The working principle of the CRISPR-Cas9 system is to artificially design two kinds of RNA: crRNA and tracrRNA, and then transform them into a single guide RNA (sgRNA), thereby guiding Cas9 to cut DNA in a targeted manner, following which cells are able to delete the target DNA through homologous and non-homologous DNA damage repair mechanisms. 6 Compared with traditional gene editing tools, such as ZFN and TALEN, the CRISPR-Cas9 technology has the advantages of simple design, ability to target any DNA sequence in the cell and to target multiple targets simultaneously, higher cutting efficiency, and lower cost. 7 At present, the CRISPR-Cas9 gene editing technology has contributed to great advancements in the clinical treatment of diseases. Major breakthroughs have been achieved in treating hereditary diseases using this technology. [8][9][10] It was used to knock out the beta-globin gene, the pathogenic gene of β-hemoglobinopathy, and it also employed rAAV6, as a donor template, to effectively correct the disease-causing mutation of SCD through homologous recombination. 10 In addition, The CRISPR-Cas9 gene editing technology has been widely used treatment-related researches and in the establishment of disease model of many cancers, including pancreatic, lung, gastric, colon, kidney, liver, head and neck, and skin cancers. [11][12][13][14][15][16][...

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CD71+ Population Enriched by HPV-E6 Protein Promotes Cancer Aggressiveness and Radioresistance in Cervical Cancer Cells

Cited by 16 publications

References 32 publications

Polyploid Giant Cancer Cells, a Hallmark of Oncoviruses and a New Therapeutic Challenge

Polyploid Giant Cancer Cells, a Hallmark of Oncoviruses and a New Therapeutic Challenge

Description of CRISPR-Cas9 development and its prospects in human papillomavirus-driven cancer treatment

Applications of CRISPR‐Cas9 in gynecological cancer research

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