The Telomerase and Alternative Lengthening of Telomeres Mechanisms Regulate Laryngeal Cancer Cell Apoptosis via the PI3K/Akt Pathway

Wang, Fei; Sheng, Jing; Cai, Lei; Xu, Yong; Liao, Hua; Tao, Zezhang

doi:10.1159/000489461

Cited by 5 publications

(3 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…PI3K/AKT axis is a crucial participant in metastasis of tumors [26]. To examine the role of HMGB1 on the PI3K/AKT axis, Western blot analysis was carried out, showing that phosphorylated AKT was promoted in MCF-7 cells via elevated HMGB1 expression in comparison to vector control (Figure 4A, 4B).…”

Section: Resultsmentioning

confidence: 99%

High-Mobility Group Box 1 (HMGB1) Promotes Angiogenesis and Tumor Migration by Regulating Hypoxia-Inducible Factor 1 (HIF-1α) Expression via the Phosphatidylinositol 3-Kinase (PI3K)/AKT Signaling Pathway in Breast Cancer Cells

Wang

Chen

et al. 2019

Med Sci Monit

View full text Add to dashboard Cite

Background High-mobility group box 1 (HMGB1) is an essential contributor towards initiation and progression of many kinds of cancers. Nevertheless, our understanding of the molecular etiology of HMGB1-modulated vasculogenesis, as well as invasion, of breast cancer is poor. This study explored HMGB1 expression in breast cancer and its role in the development and spread of malignancy. Material/Methods We enrolled 15 patients with breast cancer who received primary surgery at the Department of Thyroid and Breast Surgery in our hospital. HMGB1 was recorded and analyzed. Results Our investigation successfully proves that HMGB1 is upregulated in breast cancer tissues in comparison to the surrounding non-malignant tissues. HMGB1 enhanced vessel formation in breast cancer tissues by regulating hypoxia-inducible factor 1 (HIF-1α), which in turn upregulates the expression of VEGF. Furthermore, HMGB1-mediated upregulation of HIF-1α relies on its ability to stimulate the phosphatidylinositol 3-kinase (PI3K) pathway to reinforce AKT subunit phosphorylation. HMGB1 overexpression reinforces the vasculogenesis in malignancies not only in vivo but also in vitro . Additionally, shRNA knockdown of HMGB1 prohibited the vessel-forming and invasive capabilities, downregulated VEGF and HIF-1α, and suppressed AKT phosphorylation in breast cancer cells. Most importantly, PI3K/AKT axis suppression eliminated the effect of HMGB1-modulated vascularization and invasion in breast cancer cells. Conclusions Our research indicates that HMGB1 serves as a crucial regulator of malignant cell-modulated vessel formation and is involved in the development of malignancy. Our findings indicate that HMGB1 is a promising target for breast cancer treatment.

show abstract

Section: Resultsmentioning

confidence: 99%

High-Mobility Group Box 1 (HMGB1) Promotes Angiogenesis and Tumor Migration by Regulating Hypoxia-Inducible Factor 1 (HIF-1α) Expression via the Phosphatidylinositol 3-Kinase (PI3K)/AKT Signaling Pathway in Breast Cancer Cells

Wang

Chen

et al. 2019

Med Sci Monit

View full text Add to dashboard Cite

show abstract

“…Telomeres function as ‘caps’ to protect eukaryotic chromosomes from DNA damage and degradation [ 8 , 9 ]. The shortening of telomeres caused by incomplete replication during cell division and the attack of nucleases and other factors tends to elicit the DNA damage response, thus resulting in cell senescence and apoptosis [ 10 , 11 ].…”

Section: Introductionmentioning

confidence: 99%

hTERT promoter methylation promotes small cell lung cancer progression and radiotherapy resistance

Zhai

Zheng

et al. 2020

Journal of Radiation Research

View full text Add to dashboard Cite

Small cell lung cancer (SCLC) has been a devastating actuality in clinic and the molecular mechanisms underlying this disease remain unclear. The epigenetic alterations located in the promoter region of human telomerase reverse transcriptase (hTERT) have been demonstrated as one of the most prevalent non-coding genomic modifications in multiple cancers. However, alteration of hTERT promoter methylation in SCLC and the subsequently induced change in tumor cell behavior remains unclear. In this research, we hypothesized that abnormal methylation of hTERT promotor enhanced the progression of SCLC and the outcome of radiotherapy resistance. Quantitative real-time PCR and western blot assays were performed to evaluate the RNA and protein levels of hTERT and enhancer of zeste homolog 2 (EZH2), respectively. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was used to estimate the viability and X-ray sensitivity of H20 and H446 cell lines. Functionally, upregulation of hTERT promoted the proliferation and migration of H20 and H446 cells, and the high-level of methylation in the promoter region of hTERT induced by radiation caused radio-resistance in SCLC. Mechanically, methylation of hTERT promoter enhanced the progression and radio-resistance of SCLC through upregulating the expression of its downstream effector EZH2.

show abstract

“…Roles of apoptosis in anti-tumor effects have been investigated in many different cancers, such as cervical cancer and Epstein-Barr virus (EBV)-positive B lymphocytes [111]. Suppression of telomere-related genes through telomerase and ALT mechanisms prevents development of laryngeal squamous cell carcinoma by facilitating cell apoptosis through a mechanism involving the PI3K/Akt pathway [112], which may provide a potential therapeutic strategy via promoting apoptosis. G-quadruplex ligands have been indicated to disturb telomere replication, with an anti-proliferative result [113,114].…”

Section: Potential Therapeutic Strategy Targeting Altmentioning

confidence: 99%

Alternative Lengthening of Telomeres (ALT) in Tumors and Pluripotent Stem Cells

Zhao

Feng

Liu

2019

Genes

View full text Add to dashboard Cite

A telomere consists of repeated DNA sequences (TTAGGG)n as part of a nucleoprotein structure at the end of the linear chromosome, and their progressive shortening induces DNA damage response (DDR) that triggers cellular senescence. The telomere can be maintained by telomerase activity (TA) in the majority of cancer cells (particularly cancer stem cells) and pluripotent stem cells (PSCs), which exhibit unlimited self-proliferation. However, some cells, such as telomerase-deficient cancer cells, can add telomeric repeats by an alternative lengthening of the telomeres (ALT) pathway, showing telomere length heterogeneity. In this review, we focus on the mechanisms of the ALT pathway and potential clinical implications. We also discuss the characteristics of telomeres in PSCs, thereby shedding light on the therapeutic significance of telomere length regulation in age-related diseases and regenerative medicine.

show abstract

The Telomerase and Alternative Lengthening of Telomeres Mechanisms Regulate Laryngeal Cancer Cell Apoptosis via the PI3K/Akt Pathway

Cited by 5 publications

References 41 publications

High-Mobility Group Box 1 (HMGB1) Promotes Angiogenesis and Tumor Migration by Regulating Hypoxia-Inducible Factor 1 (HIF-1α) Expression via the Phosphatidylinositol 3-Kinase (PI3K)/AKT Signaling Pathway in Breast Cancer Cells

High-Mobility Group Box 1 (HMGB1) Promotes Angiogenesis and Tumor Migration by Regulating Hypoxia-Inducible Factor 1 (HIF-1α) Expression via the Phosphatidylinositol 3-Kinase (PI3K)/AKT Signaling Pathway in Breast Cancer Cells

hTERT promoter methylation promotes small cell lung cancer progression and radiotherapy resistance

Alternative Lengthening of Telomeres (ALT) in Tumors and Pluripotent Stem Cells

Contact Info

Product

Resources

About