British Journal of Cancer: Eat while it's hot, it will cause cancer

Esophageal cancer is one of the most common malignant tumors, which seriously threatens the life and health of resident.

It is known that the incidence and progression of esophageal cancer are related to polygenic abnormalities, and external environmental factors, especially high-temperature diet, are considered to be one of the main risk factors for esophageal squamous cell carcinom.

Recently, the team of Li Zhiyuan from Guangzhou Institute of Biomedicine and Health, Chinese Academy of Sciences published a research paper entitled: Thermal stress involved in TRPV2 promotes tumorigenesis through the pathways of HSP70/27 and PI3K/Akt/mTOR in esophageal squamous cell carcinoma in the British Journal of Cance.

This study is the first to find that the transient receptor potential ion channel vanilloid subtype 2 (TRPV2) can be activated by repeated heat or agonist action to activate the HSP70/27 and PI3K/Akt/mTOR signaling pathways, which can significantly promote esophageal squamous cell carcinoma cells in vitro The malignant behavior of esophageal squamous cell carcinoma can significantly promote the tumorigenesis and spread of esophageal squamous cell carcinoma in viv.

Based on years of research on transient receptor potential ion channels (TRP), Li Zhiyuan's research team detected the expression and function of heat-sensitive TRPV in human esophageal squamous epithelial cells, and found that esophageal squamous cell carcinoma (ESCC) TRPV2 expression was significantly upregulated in both cellular and clinical ESCC samples, and calcium imaging experiments confirmed a corresponding increase in its functional activit.

Further studies have found that short and frequent stimulation of ESCC cells with heat (54°C) that activates TRPV2 channels can significantly enhance malignant cell behaviors such as ESCC cell proliferation, invasion, and angiogenesis in vitro, while in viv.

Mechanistically, TRPV2 can up-regulate heat shock factor 1 (HSF1) and promote the transcriptional expression of heat shock proteins 70 and 27 (HSP70/27) after ESCC cells are activated by heat stress, thereby promoting the tumorigenicity of ESCC; At the same time, PI3K is significantly activated in this process, which in turn activates its downstream signaling protein PDK1, and then PDK1 upregulates the functions of target proteins AKT1 and mTORC Conversely, the negative regulator of PI3K, PTEN, is downregulated and inhibited, indicating that PI3K signaling is amplified by PTEN, thereby significantly increasing PI3K signalin.

Schematic diagram of the involvement of heat stress in TRPV2 in promoting tumorigenesis of esophageal squamous cell carcinoma

The study also found that pan-PI3K/mTOR kinase inhibitors VS5584 and Oroxin B can significantly inhibit the proliferation of ESCC cells overactivated by TRPV2, and the combination of the two with Tranilast can further weaken the proliferation ability of ESCC cells, suggesting that Tranilast combined with pan-PI3K/ mTOR inhibitors may be useful in the treatment of ESC.

It is worth noting that the activation temperature of the TRPV2 channel found in this study is 54°C, which is lower than the dietary temperature in many populations and well below the high temperature dietary risk temperature recommended by the International Agency for Research on Cancer (65°C), so the study A new direction is proposed for the prevention and treatment of esophageal squamous cell carcinom.

Original source:

Huang, .