Pin2 telomeric repeat factor 1-interacting telomerase inhibitor 1 (PinX1) inhibits nasopharyngeal cancer cell stemness: implication for cancer progression and therapeutic targeting

Yu, Chaosheng; Chen, Fang; Wang, Xiaoqi; Cai, Zhimou; Yang, Mengxue; Zhong, Qingwen; Feng, Jialian; Li, Junzheng; Shen, Changwei; Wen, Zhong

doi:10.1186/s13046-020-1530-3

Cited by 12 publications

(7 citation statements)

References 42 publications

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“…Furthermore, ~80% lung cancer cases are non-small cell lung cancer (NSCLC), and lung adenocarcinoma is the most common subtype of NSCLC ( 1 ). Tumor metastasis is the main cause of clinical treatment failure and mortality ( 2 ). Lung adenocarcinoma is a type of lung cancer that easily metastasizes.…”

Section: Introductionmentioning

confidence: 99%

Crosstalk between H1975 tumor cells and platelets to induce the proliferation, migration and tube formation of vascular endothelial cells

Dong

Zhu

et al. 2021

Oncol Lett

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Activated platelets (PLTs) participate in the regulation of tumor angiogenesis, and tumors can activate PLTs. Whether co-culture of lung carcinoma with PLTs improves the function of human umbilical vein endothelial cells (HUVECs) requires further investigation. The present study aimed to investigate the impact of H1975 cell crosstalk with PLTs on the proliferation, migration and tube formation of HUVECs. Following generation of cell-derived supernatants and construction of the co-culture system, Cell Counting Kit-8, flow cytometry, transmission electron microscopy and a meter for epithelial measurement were performed to detect the proliferative ability of HUVECs. Furthermore, the wound healing and Transwell migration assays were performed to detect the migratory ability of HUVECs. A tube formation assay was performed to assess angiogenesis, ELISA was applied to detect the content of vascular endothelial growth factor (VEGF) and western blotting was carried out to measure the expression levels of VEGF receptor 2 (VEGFR2) in HUVECs. Compared with single-cultured HUVECs (control), co-culture with H1975 cells and PLTs (Exp_HP) improved cell proliferation, increased the proportion of cells in the S-phase, destroyed the cell ultrastructure and decreased transepithelial electrical resistance in HUVECs. In addition, a higher relative migration rate, greater number of migrated cells, stronger tube-forming ability and increased expression of VEGF and VEGFR2 were detected in the Exp_HP group compared with the control group. The properties of HUVECs in Exp_H (co-cultured with H1975 cells) were similar to those in Exp_HP, but significantly weaker. Taken together, the results of the present study suggest that tumor cells interacting with PLTs may play an important role in tumor angiogenesis by affecting or mediating changes in the properties of vascular endothelial cells (VECs).

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Section: Introductionmentioning

confidence: 99%

Crosstalk between H1975 tumor cells and platelets to induce the proliferation, migration and tube formation of vascular endothelial cells

Dong

Zhu

et al. 2021

Oncol Lett

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“… 101 As a tumor suppressor gene, Pin2 telomeric repeat factor 1-interacting telomerase inhibitor 1 (PinX1) inhibits cell proliferation, migration, and invasion by regulating p53/miR-200b-mediated transcriptional inhibition of Snail1, Twist1, and Zeb1, thereby inhibiting EMT of CD133(+) cancer stem cells (CSCs) in NPC. 102 Furthermore, Zhao et al 103 found that cisplatin treatment can induce the upregulation of miR-125a and miR-125b expression, and these miRNAs can target p53 mRNA and reduce p53 protein-induced apoptosis, which may be one of the causes of cisplatin resistance in NPC cells.…”

Section: Crucial Signal Pathways Related To Targeted Therapy Of Npcmentioning

confidence: 99%

Advances in targeted therapy mainly based on signal pathways for nasopharyngeal carcinoma

Kang

Ren

et al. 2020

Sig Transduct Target Ther

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Nasopharyngeal carcinoma (NPC) is a malignant epithelial carcinoma of the head and neck region which mainly distributes in southern China and Southeast Asia and has a crucial association with the Epstein–Barr virus. Based on epidemiological data, both incidence and mortality of NPC have significantly declined in recent decades grounded on the improvement of living standard and medical level in an endemic region, in particular, with the clinical use of individualized chemotherapy and intensity-modulated radiotherapy (IMRT) which profoundly contributes to the cure rate of NPC patients. To tackle the challenges including local recurrence and distant metastasis in the current NPC treatment, we discussed the implication of using targeted therapy against critical molecules in various signal pathways, and how they synergize with chemoradiotherapy in the NPC treatment. Combination treatment including targeted therapy and IMRT or concurrent chemoradiotherapy is presumably to be future options, which may reduce radiation or chemotherapy toxicities and open new avenues for the improvement of the expected functional outcome for patients with advanced NPC.

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“…We have previously reported roles for PinX1 in modulating proliferation, apoptosis, EMT, and stemness in NPC cells 19 . Here, we investigated the mechanisms whereby PinX1 in uences proliferation, apoptosis, and autophagy in NPC cells.…”

Section: Discussionmentioning

confidence: 97%

PinX1-Induced Autophagy Inhibits Cell Proliferation and Induces Cell Apoptosis by Inhibiting the NF-κB/p65 Signaling Pathway in Nasopharyngeal Carcinoma

Yang¹,

Chen²,

Yu³

et al. 2021

Preprint

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BackgroundThe role of PinX1 in tumorigenesis and development has been extensively studied. We have previously reported roles for PinX1 in modulating proliferation, apoptosis, EMT, and stemness in NPC cells. However, the relationship between PinX1, autophagy, and cell function in NPC remains unclear. The aim of this study was to explore the mechanisms by which PinX1 regulates autophagy in NPC, and to investigate its clinical significance and biological role with respect to disease progression. MethodsMTT and xenograft tumorigenicity assays were used to assess the proliferative capacity of NPC cells. Autophagic flux was monitored using a tandem monomeric DAPI–FITC–LC3 reporter assay. The rates of apoptosis and the cell cycle in NPC cells were analyzed using flow cytometry. Reverse-transcription quantitative PCR was used to evaluate the expression of hTERT and PinX1. Western blot analysis was used to evaluate the activation of autophagy and the signaling status of the AKT/mTOR and NF-κB/p65 pathways. ResultsPinX1 overexpression induced autophagy and apoptosis, while suppressing NPC cell proliferation, migration, and invasion, and decelerated cell-cycle progression; inhibiting autophagy via 3-methyladenine reversed these outcomes. Mechanistic investigations clarified that PinX1 overexpression significantly reduced the expression of p-AKT, p-mTOR, p65, and p-p65. Chloroquine treatment in PinX1-overexpressing cells did not significantly alter p-AKT and p-mTOR levels, whereas 3-MA treatment in PinX1-overexpressing cells resulted in increased p65 and p-p65 expression, relative to untreated PinX1-overexpressing cells.ConclusionThese findings indicate that PinX1 promotes autophagy by inhibiting the AKT/mTOR signaling pathway; this, in turn, inhibits the NF-κB/p65 signaling pathway, thereby inhibiting cell proliferation and induces cell apoptosis in NPC cells.

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Pin2 telomeric repeat factor 1-interacting telomerase inhibitor 1 (PinX1) inhibits nasopharyngeal cancer cell stemness: implication for cancer progression and therapeutic targeting

Cited by 12 publications

References 42 publications

Crosstalk between H1975 tumor cells and platelets to induce the proliferation, migration and tube formation of vascular endothelial cells

Crosstalk between H1975 tumor cells and platelets to induce the proliferation, migration and tube formation of vascular endothelial cells

Advances in targeted therapy mainly based on signal pathways for nasopharyngeal carcinoma

PinX1-Induced Autophagy Inhibits Cell Proliferation and Induces Cell Apoptosis by Inhibiting the NF-κB/p65 Signaling Pathway in Nasopharyngeal Carcinoma

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