Activation of P2×7 Receptor Promotes the Invasion and Migration of Colon Cancer Cells via the STAT3 Signaling

Zhang, Wenjun; Hu, Cegui; Luo, Haiwei; Zhu, Zhengming

doi:10.3389/fcell.2020.586555

Cited by 19 publications

(13 citation statements)

References 50 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Activation and phosphorylation of STAT3 could markedly promote the proliferation and metastasis of SW480 cells, and enhance tumorigenesis ( 42 ). In one study, the migration and invasion of colon cancer cells was promoted, possibly via the activation of the STAT3 pathway ( 43 ). Therefore, it was hypothesized that propofol may promote CRC cell ferroptosis via targeting STAT3.…”

Section: Discussionmentioning

confidence: 99%

Propofol induces the ferroptosis of colorectal cancer cells by downregulating STAT3 expression

Zhao

Chen

2021

Oncol Lett

View full text Add to dashboard Cite

Propofol is a commonly used intravenous anesthetic agent that can also suppress the proliferation of various human cancer types, including colorectal cancer (CRC). The present study aimed to investigate whether propofol could induce the ferroptosis of CRC cells by regulating signal transducer and activator of transcription 3 (STAT3). STAT3 expression in normal and CRC tissues was measured. Human normal colonic epithelial NCM460 cells and human CRC SW480 cells were exposed to different concentrations of propofol and then cell viability was detected. SW480 cells were transfected with a vector overexpressing STAT3 and treated with propofol, and the cell viability, colony formation, cell proliferation, iron level, ROS production and ferroptosis of these cells and control cells were evaluated. Overall, the results showed that STAT3 was highly expressed in CRC tissues. Propofol exerted no marked effect on NCM460 cell viability, but inhibited SW480 cell viability in a concentration-dependent manner. Meanwhile, STAT3 was downregulated by propofol in a concentration-dependent manner. Propofol also inhibited CRC cell proliferation and colony formation, and enhanced cellular iron and ROS levels. Additionally, the expression of proteins involved in ferroptosis was also altered by propofol, including the upregulation of CHAC1 and PTGS2 expression in CRC cells, and the inhibition of GPX4 expression. However, STAT3 overexpression blocked the effect of propofol on CRC cells. In conclusion, propofol may trigger the ferroptosis of CRC cells by downregulating STAT3 expression.

show abstract

Section: Discussionmentioning

confidence: 99%

Propofol induces the ferroptosis of colorectal cancer cells by downregulating STAT3 expression

Zhao

Chen

2021

Oncol Lett

View full text Add to dashboard Cite

show abstract

“…The cell migration ability was assessed using the scratch-wound healing assay [ 25 ]. The width of the wound bed was recorded at 0, 24, and 48 hours after the scratch wound.…”

Section: Methodsmentioning

confidence: 99%

SLCO1B3 promotes colorectal cancer tumorigenesis and metastasis through STAT3

Zhi

Zhao

Zhang

et al. 2021

Aging

View full text Add to dashboard Cite

Solute carrier organic anion transporter family member 1B3 (SLCO1B3) is a gene that encodes an organic anion-transporting polypeptide (OATP) 1B3, a membrane-bound multi-specific transporter in hepatocytes. SLCO1B3 was first reported in hepatocytes. Later, it was found that its expression is higher in colorectal cancer (CRC) than in the adjacent normal tissue. However, the role of SLCO1B3 in CRC is not well elucidated. In this study, the correlation between SLCO1B3 and the overall survival (OS) of CRC patients was evaluated using data from the GEO database. This study evaluated the relationship between SLCO1B3 and the clinicopathological characteristics and prognosis of CRC patients. The effects of SLCO1B3 knockdown, on human CRC cell proliferation, migration, and invasion in vitro and CRC tumorigenesis and metastasis in vivo were also examined. In addition, next-generation sequencing was used to identify SLCO1B3 mediators. The results confirmed the association between SLCO1B3 and poor OS of CRC patients, and SLCO1B3 was identified as the top hub gene associated with the OS. The study showed that high SLCO1B3 expression was associated with poor tumor differentiation, advanced disease stage, tumor invasion, lymph node metastasis, and poor OS. Next-generation sequencing revealed that SLCO1B3 knockdown affected the expression of several genes involved in cancer invasion, metastasis, and DNA repair. Moreover, the western blot analysis showed that SLCO1B3 knockdown downregulated p-STAT3, MMP-2, and MMP-9. In summary, we demonstrated that SLCO1B3 acts as a novel carcinogen in the CRC that drives the CRC tumorigenesis and metastasis. SLCO1B3 inhibitors, alone or in combination with current drugs, may have therapeutic benefits in CRC.

show abstract

“…Two studies recently correlated high expression of P2X7R in colorectal cancer with poor prognosis, cancer progression, and metastasis, thus suggesting that P2X7R might be exploited as a biomarker and therapeutic target in these patients ( Zhang et al, 2019b ; Calik et al, 2020b ). P2X7R might promote the migration and invasion of colon cancer cells by activating the STAT3 pathway ( Zhang et al, 2020 ). Moreover, high expression of P2X7R was associated to poor survival in gastric cancer patients, suggesting that P2X7R may serve as a prognostic parameter and therapeutic target also in these patients ( Calik et al, 2020a ).…”

Section: The P2x7r In Tumor Cellsmentioning

confidence: 99%

The P2X7 Receptor in Tumor Immunity

Grassi

Conti

2021

Front. Cell Dev. Biol.

View full text Add to dashboard Cite

Extracellular adenosine triphosphate (eATP) is a potent mediator of the immune response via stimulation of purinergic P2 receptors. ATP concentration in the extracellular space increases dramatically during tissue damage and eATP acts as a danger-associated molecular pattern (DAMP) to alert innate immune system cells for tissue repair. Similarly, eATP is present at hundreds of micromolar concentration in the tumor microenvironment (TME). However, its impact on antitumor immune response is still not well established, probably because of the complexity of the responses it induces in different cells constituting the TME. On one hand, ATP released by tumor cells concomitantly to cell death can contribute to immunogenic cell death (ICD) that is proinflammatory for the innate immune compartment and beneficial for tumor control, while on the other hand, eATP can foster immune-suppressive mechanisms within the TME, thus contributing to tumor progression and metastasis. It is well established that T-cell immunity is pivotal in limiting tumor growth and possibly eradicating neoplastic cells. T cells are limited though in their antitumor activity through different mechanisms, such as exhaustion, anergy, and senescence; the pathways resulting in these cellular outcomes are not clear. Here, we review the function of P2X7 receptor in conditioning T cell-dependent immunity against cancer.

show abstract

Activation of P2×7 Receptor Promotes the Invasion and Migration of Colon Cancer Cells via the STAT3 Signaling

Cited by 19 publications

References 50 publications

Propofol induces the ferroptosis of colorectal cancer cells by downregulating STAT3 expression

Propofol induces the ferroptosis of colorectal cancer cells by downregulating STAT3 expression

SLCO1B3 promotes colorectal cancer tumorigenesis and metastasis through STAT3

The P2X7 Receptor in Tumor Immunity

Contact Info

Product

Resources

About