Panx1 promotes invasion-metastasis cascade in hepatocellular carcinoma

Shi, Guangjun; Liu, Chuanliang; Yang, Yiming; Song, Lan; Liu, Xueni; Wang, Chuanxu; Peng, Zhihai; Li, Hao; Zhong, Lin

doi:10.7150/jca.32986

Cited by 17 publications

(19 citation statements)

References 20 publications

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“…Of note, NOTCH2NL is an oncogene activating Notch signaling by direct interaction with NOTCH2, thereby promoting proliferation and self-renewal [ 40 ]. PANX1 overexpression has been associated with a worse prognosis in breast and liver cancer patients, which mechanistically is linked to PANX1-dependent enhancement of epithelial–mesenchymal transition and thus cell invasion [ 41 , 42 ]. PVT1 is a long noncoding RNA that is commonly overexpressed in breast cancer and has been implicated in the regulation of MYC oncogene [ 43 , 44 ], while JAK2 is a tyrosine kinase activating cancer-driving JAK/STAT signaling pathway [ 45 ].…”

Section: Resultsmentioning

confidence: 99%

Pterostilbene Changes Epigenetic Marks at Enhancer Regions of Oncogenes in Breast Cancer Cells

et al. 2021

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Epigenetic aberrations are linked to sporadic breast cancer. Interestingly, certain dietary polyphenols with anti-cancer effects, such as pterostilbene (PTS), have been shown to regulate gene expression by altering epigenetic patterns. Our group has proposed the involvement of DNA methylation and DNA methyltransferase 3B (DNMT3B) as vital players in PTS-mediated suppression of candidate oncogenes and suggested a role of enhancers as target regions. In the present study, we assess a genome-wide impact of PTS on epigenetic marks at enhancers in highly invasive MCF10CA1a breast cancer cells. Following chromatin immunoprecipitation (ChIP)-sequencing in MCF10CA1a cells treated with 7 μM PTS for 9 days, we discovered that PTS leads to increased binding of DNMT3B at enhancers of 77 genes, and 17 of those genes display an overlapping decrease in the occupancy of trimethylation at lysine 36 of histone 3 (H3K36me3), a mark of active enhancers. We selected two genes, PITPNC1 and LINC00910, and found that their enhancers are hypermethylated in response to PTS. These changes coincided with the downregulation of gene expression. Of importance, we showed that 6 out of 17 target enhancers, including PITPNC1 and LINC00910, are bound by an oncogenic transcription factor OCT1 in MCF10CA1a cells. Indeed, the six enhancers corresponded to genes with established or putative cancer-driving functions. PTS led to a decrease in OCT1 binding at those enhancers, and OCT1 depletion resulted in PITPNC1 and LINC00910 downregulation, further demonstrating a role for OCT1 in transcriptional regulation. Our findings provide novel evidence for the epigenetic regulation of enhancer regions by dietary polyphenols in breast cancer cells.

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Section: Resultsmentioning

confidence: 99%

Pterostilbene Changes Epigenetic Marks at Enhancer Regions of Oncogenes in Breast Cancer Cells

et al. 2021

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“…In this study, we investigated PANX1 expression levels and prognostic landscape in various cancer. Previous studies showed that PANX1 was overexpressed in hepatocellular carcinoma (HCC) [ 52 ], gastric cancer cells [ 53 ], and melanoma cells [ 7 ]. However, the expression patterns of PANX1 in other tumors are unknown.…”

Section: Discussionmentioning

confidence: 99%

“…Only a few studies have been conducted to determine the PANX1’s prognostic power in cancer. A previous study reported that high PANX1 expression predicts a poor prognosis of HCC [ 52 ]. In the present study, the Kaplan Meier plotter results showed that high PANX1 expression was associated with a poor prognosis in patients with KIRP, LUAD, UCEC, and PAAD.…”

Section: Discussionmentioning

confidence: 99%

PANX1 is a potential prognostic biomarker associated with immune infiltration in pancreatic adenocarcinoma: A pan-cancer analysis

2021

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“…The cell-surface channel protein pannexin-1 (PANX1), the role of which in metastatic progression has been previously reported, 51,52 provides an example of how a mechanosensitive channel can regulate CTC survival in the microcirculation. Furlow et al demonstrated that metastatic breast cancer cells with a PANX1 channel-activating mutation gained a survival advantage due to an increase in the release of ATP, which was modulated via PANX1 when the breast cancer cells became lodged in the microvasculature.…”

Section: Mechanosensitive Channels That Can Drive Cancer Progressionmentioning

confidence: 99%

Squeezing through the microcirculation: survival adaptations of circulating tumour cells to seed metastasis

Paizal

Bakal

2020

Br J Cancer

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During metastasis, tumour cells navigating the vascular circulatory system—circulating tumour cells (CTCs)—encounter capillary beds, where they start the process of extravasation. Biomechanical constriction forces exerted by the microcirculation compromise the survival of tumour cells within capillaries, but a proportion of CTCs manage to successfully extravasate and colonise distant sites. Despite the profound importance of this step in the progression of metastatic cancers, the factors about this deadly minority of cells remain elusive. Growing evidence suggests that mechanical forces exerted by the capillaries might induce adaptive mechanisms in CTCs, enhancing their survival and metastatic potency. Advances in microfluidics have enabled a better understanding of the cell-survival capabilities adopted in capillary-mimicking constrictions. In this review, we will highlight adaptations developed by CTCs to endure mechanical constraints in the microvasculature and outline how these mechanical forces might trigger dynamic changes towards a more invasive phenotype. A better understanding of the dynamic mechanisms adopted by CTCs within the microcirculation that ultimately lead to metastasis could open up novel therapeutic avenues.

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Panx1 promotes invasion-metastasis cascade in hepatocellular carcinoma

Cited by 17 publications

References 20 publications

Pterostilbene Changes Epigenetic Marks at Enhancer Regions of Oncogenes in Breast Cancer Cells

Pterostilbene Changes Epigenetic Marks at Enhancer Regions of Oncogenes in Breast Cancer Cells

PANX1 is a potential prognostic biomarker associated with immune infiltration in pancreatic adenocarcinoma: A pan-cancer analysis

Squeezing through the microcirculation: survival adaptations of circulating tumour cells to seed metastasis

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