Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Cellular and Molecular Biology

Thermal stress involved in TRPV2 promotes tumorigenesis through the pathways of HSP70/27 and PI3K/Akt/mTOR in esophageal squamous cell carcinoma

British Journal of Cancer volume 127, pages 1424–1439 (2022)Cite this article

Subjects

Abstract

Background

The transient receptor potential vanilloid receptor 2 (TRPV2) has been found to participate in the pathogenesis of various types of cancers, however, its role(s) in the tumorigenesis of ESCC remain poorly understood.

Methods

Western blotting and immunohistochemistry were performed to determine the expression profiles of TRPV2 in the ESCC patient tissues. A series of in vitro and in vivo experiments were conducted to reveal the role of TRPV2 in the tumorigenesis of ESCC.

Results

Our study first uncovered that the activation of TRPV2 by recurrent acute thermal stress (54 °C) or O1821 (20 μM) promoted cancerous behaviours in ESCC cells. The pro-angiogenic capacity of the ESCC cells was found to be enhanced profoundly and both tumour formation and metastasis that originated from the cells were substantially promoted in nude mouse models upon the activation of TRPV2. These effects were inhibited significantly by tranilast (120 μM) and abolished by TRPV2 knockout. Conversely, overexpression of TRPV2 could switch the cells to tumorigenesis upon activation of TRPV2. Mechanistically, the driving role of TRPV2 in the progression of ESCC is mainly regulated by the HSP70/27 and PI3K/Akt/mTOR signalling pathways.

Conclusions

We revealed that TRPV2-PI3K/Akt/mTOR is a novel and promising target for the prevention and treatment of ESCC.

This is a preview of subscription content, access via your institution

Relevant articles

Open Access articles citing this article.

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

Learn more

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: TRPV2 is upregulated in ESCC cells, and overactivation of TRPV2 promotes cellular proliferation.
Fig. 2: Overactivation of TRPV2 promotes the migration and invasion of ESCC and ectopically expressed TRPV2 NE2 cells.
Fig. 3: Overactivation of TRPV2 in ESCC cells promotes tumour-associated angiogenesis.
Fig. 4: Overactivation of TRPV2 promotes ESCC formation and invasion in nude mice.
Fig. 5: TRPV2 activation mediates HSP and PI3K signalling pathways.
Fig. 6: TRPV2 expression profile in ESCC patients.
Fig. 7: High expression level of TRPV2 was associated with worse survival in ESCC.

Data availability

The data in this study are available from the corresponding author upon reasonable request.

References

  1. Florea A, Sangaré L, Lowe K. A multinational assessment of gastric, esophageal, and colorectal cancer burden: a report of disease incidence, prevalence, and fatality. J Gastrointest Cancer. 2020;51:965–71.

    Article  PubMed  Google Scholar 

  2. Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM. Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer. 2010;127:2893–917.

    Article  PubMed  CAS  Google Scholar 

  3. Ma G, Zhang J, Jiang H, Zhang N, Zhu Y, Deng Y, et al. Microvessel density as a prognostic factor in esophageal squamous cell cancer patients: a meta-analysis. Medicine. 2017;96:e7600.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Domper Arnal MJ, Ferrández Arenas Á, Lanas Arbeloa Á. Esophageal cancer: risk factors, screening and endoscopic treatment in Western and Eastern countries. World J Gastroenterol. 2015;21:7933–43.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Castellsagu´e X, Munoz N, Stefani E. Influence of mate drinking, hot beverages and diet on esophageal cancer risk in south America. Int J Cancer. 2000;88:658–64.

    Article  Google Scholar 

  6. Song Q, Jiang D, Wang H, Huang J, Liu Y, Xu C, et al. Chromosomal and genomic variations in esophageal squamous cell carcinoma: a review of technologies, applications, and prospections. J Cancer. 2017;8:2492–2500.

    Article  PubMed  PubMed Central  Google Scholar 

  7. McCormack VA, Menya D, Munishi MO, Dzamalala C, Gasmelseed N, Leon Roux M, et al. Informing etiologic research priorities for squamous cell esophageal cancer in Africa: a review of setting-specific exposures to known and putative risk factors. Int J Cancer. 2017;140:259–71.

    Article  PubMed  CAS  Google Scholar 

  8. Islami F, Boffetta P, Ren JS, Pedoeim L, Khatib D, Kamangar F. High-temperature beverages and foods and esophageal cancer risk-a systematic review. Int J Cancer. 2009;125:491–524.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  9. Siegel R, Naishadham D, Jemal A. Cancer statistics. CA Cancer J Clin. 2012;62:10–29.

    Article  PubMed  Google Scholar 

  10. Enzinger PC, Mayer RJ. Esophageal cancer. N. Engl J Med. 2003;349:2241–52.

    Article  PubMed  CAS  Google Scholar 

  11. Abnet CC, Arnold M, Wei WQ. Epidemiology of esophageal squamous cell carcinoma. Gastroenterology. 2018;154:360–73.

    Article  PubMed  Google Scholar 

  12. Lin S, Xu G, Chen Z, Liu X, Li J, Ma L, et al. Tea drinking and the risk of esophageal cancer: focus on tea type and drinking temperature. Eur J Cancer Prev. 2020; e-pub ahead of print; https://doi.org/10.1097/CEJ.0000000000000568.

  13. Gao Y, Hu N, Han XY, Ding T, Giffen C, Goldstein AM, et al. Risk factors for esophageal and gastric cancers in Shanxi Province, China: a case-control study. Cancer Epidemiol. 2011;35:e91–99.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Tai WP, Nie GJ, Chen MJ, Yaz TY, Guli A, Wuxur A, et al. Hot food and beverage consumption and the risk of esophageal squamouscell carcinoma: a case-control study in a northwest area in China. Medicine. 2017;96:e9325.

    Article  PubMed  PubMed Central  Google Scholar 

  15. Loomis D, Guyton KZ, Grosse Y, Lauby-Secretan B, El Ghissassi F, Bouvard V, et al. International Agency for Research on Cancer Monograph Working Group, carcinogenicity of drinking coffee, mate, and very hot beverages. Lancet Oncol. 2016;17:877–8.

    Article  PubMed  Google Scholar 

  16. Okaru AO, Rullmann A, Farah A, Gonzalez de Mejia E, Stern MC, Lachenmeier DW. Comparative esophageal cancer risk assessment of hot beverage consumption (coffee, mate and tea): the margin of exposure of PAH vs very hot temperatures. BMC Cancer. 2018;18:236–46.

    Article  PubMed  PubMed Central  Google Scholar 

  17. Monet M, Lehenkyi V, Gackiere F, Firlej V, Vandenberghe M, Roudbaraki M, et al. Role of cationic channel TRPV2 in promoting prostate cancer migration and progression to androgen resistance. Cancer Res. 2010;70:1225–1235.

    Article  PubMed  CAS  Google Scholar 

  18. Elbaz M, Ahirwar D. TRPV2 is a novel biomarker and therapeutic target in triple negative breast cancer. Oncotarget. 2016;5:27–39.

    Google Scholar 

  19. Clapham DE, Montell C, Schultz G, Julius D. International Union of Pharmacology International Union of Pharmacology XLIII Compendium of voltage-gated ion channels: transient receptor potential channels. Pharm Rev. 2003;55:591–6.

    Article  PubMed  Google Scholar 

  20. Liu G, Xie C, Sun F, Xu X, Yang Y, Zhang T, et al. Clinical significance of transient receptor potential vanilloid 2 expression in human hepatocellular carcinoma. Cancer Genet Cytogenet. 2010;197:54–59.

    Article  PubMed  CAS  Google Scholar 

  21. Islami F, Pourshams A, Nasrollahzadeh D, Kamangar F, Fahimi S, Shakeri R, et al. Tea drinking habits, esophageal cancer in a high risk area in northern Iran: population based case–control study. BMJ. 2009;338:b929.

  22. Michael OM, Rachel H, Oscar M, Theonest N, Arnold N, Joachim S, et al. Africa’s esophageal cancer corridor: do hot beverages contribute? Cancer Causes Control. 2015;26:1477–86.

    Article  Google Scholar 

  23. Islami F, Boffetta P, Ren JS, Pedoeim L, Khatib D, Kamangar F. High-temperature beverages and foods and esophageal cancer risk—a systematic review. Int J Cancer. 2009;125:491–524.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  24. Huang R, Wang F, Yang Y, Ma W, Lin Z, Cheng N, et al. Recurrent activations of transient receptor potential vanilloid-1 and vanilloid-4 promote cellular proliferation and migration in esophageal squamous cell carcinoma cells. FEBS Openbio. 2019;9:206–25.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  25. Ma W, Li C, Yin S, Liu J, Gao C, Lin Z, et al. Novel role of TRPV2 in promoting the cytotoxicity of H2O2-mediated oxidative stress in human hepatoma cells. Free Radic BiolMed. 2015;89:1003–13.

    Article  CAS  Google Scholar 

  26. Xie J, Ge W, Li N, Liu Q, Chen F, Yang X, et al. Efficient base editing for multiple genes and loci in pigs using base editors. Nat Commun. 2019;10:2852–65.

    Article  PubMed  PubMed Central  Google Scholar 

  27. Bae S, Park J, Kim JS. Cas-OFFinder: a fast and versatile algorithm that searches for potential off-target sites of Cas9 RNA-guided endonucleases. Bioinformatics. 2014;30:1473–5.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  28. Zhou K, Zhang SS, Yan Y, Zhao S. Overexpression of transient receptor potential vanilloid 2 is associated with poor prognosis in patients with esophageal squamous cell carcinoma. Med Oncol. 2014;31:17.

    Article  PubMed  Google Scholar 

  29. Michihiro K, Atsushi S, Yuzo Y, Keita K, Toshiyuki K, Katsutoshi S, et al. The expression and role of TRPV2 in esophageal squamous cell carcinoma. Sci Rep. 2019;9:16055.

    Article  Google Scholar 

  30. Nilius B, Owsianik G, Voets T, Peters JA. Transient receptor potential cation channels in disease. Physiol Rev. 2007;87:165–217.

    Article  PubMed  CAS  Google Scholar 

  31. West AV, Wullkopf L, Christensen A, Leijnse N, Tarp JM, Mathiesen J, et al. Dynamics of cancerous tissue correlates with invasiveness. Sci Rep. 2017;7:43800–13.

    Article  PubMed  PubMed Central  Google Scholar 

  32. Chiorazzi N, Ferrarini M. Cellular origin(s) of chronic lymphocytic leukemia: cautionary notes and additional considerations and possibilities. Blood. 2011;117:1781–91.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  33. Teresina L, Cheng K, Tanner MR, He M, Beeton C, Yousef A-A, et al. The cation channel trpv2 is a new suppressor of arthritis severity, joint damage and synovial fibroblast invasion. Clin Immunol. 2015;158:183–92.

    Article  Google Scholar 

  34. Offertaler L, Mo F-M, Biatkai S. Selective ligands and cellular effectors of a G protein-coupled endothelial cannabinoid receptor. Mol Pharmacol. 2003;63:699–705.

    Article  PubMed  CAS  Google Scholar 

  35. Shin Y, Kim H, Han S, Won J, Jeong HE, Lee ES, et al. Hydrogels: extracellular matrix heterogeneity regulates three-dimensional morphologies of breast adenocarcinoma cell invasion. advanced healthcare. Materials. 2013;2:920–920.

    CAS  Google Scholar 

  36. Huang YL, Segall JE, Wu M. Microfluidic modeling of the biophysical microenvironment in tumor cell invasion. Lab Chip. 2017;17:3221–33.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  37. Maciaczyk D, Picard D, Zhao L, Koch K, Herrera-Rios D, Li G, et al. CBF1 is clinically prognostic and serves as a target to block cellular invasion and chemoresistance of EMT-like glioblastoma cells. Br J Cancer. 2017;117:102–12.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  38. Caporali S, Amaro A, Levati L, Alvino E, Lacal PM, Mastroeni S, et al. miR-126-3p down regulation contributes to dabrafenib acquired resistance in melanoma by up-regulating ADAM9 and VEGF-A. J Exp Clin Cancer Res. 2019;38:272–88.

    Article  PubMed  PubMed Central  Google Scholar 

  39. Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell. 2011;144:646–74.

    Article  PubMed  CAS  Google Scholar 

  40. Brünnert D, Langer C, Zimmermann L, Bargou RC, Burchardt M, Chatterjee M, et al. The heat shock protein 70 inhibitor VER155008 suppresses the expression of HSP27, HOP and HSP90β and the androgen receptor, induces apoptosis, and attenuates prostate cancer cell growth. J Cell Biochem. 2020;121:407–17.

    Article  PubMed  Google Scholar 

  41. Jin HO, Hong SE, Kim JY, Kim MR, Chang YH, Hong YJ, et al. Induction of HSP27 and HSP70 by constitutive overexpression of Redd1 confers resistance of lung cancer cells to ionizing radiation. Oncol Rep. 2019;41:3119–26.

    PubMed  CAS  Google Scholar 

  42. Söderström HK, Kauppi JT, Oksala N, Paavonen T, Krogerus L, Räsänen J, et al. Overexpression of HSP27 and HSP70 is associated with decreased survival among patients with esophageal adenocarcinoma. World J Clin Cases. 2019;7:260–9.

    Article  PubMed  PubMed Central  Google Scholar 

  43. Shen J, Xiao Z, Zhao Q, Li M, Wu X, Zhang L, et al. Anti-cancer therapy with TNFα and IFNγ: A comprehensive review. Cell Prolif. 2018;51:12441.

    Article  Google Scholar 

  44. Feng Y, Chenl X, Cassady K, Zou Z, Yang S, Wang Z, et al. The role of mTOR inhibitors in hematologic disease: from bench to bedside. Front Oncol. 2021;10:10–25.

    Article  Google Scholar 

  45. Mickle AD, Shepherd AJ, Mohapatra DP. Sensory TRP channels: the key transducers of nociception and pain. Prog Mol Biol Transl Sci. 2015;131:73–118.

    Article  PubMed  PubMed Central  Google Scholar 

  46. Benham CD, Gunthorpe MJ, Davis JB. TRPV channels as temperature sensors. Cell Calcium. 2003;33:479–87.

    Article  PubMed  CAS  Google Scholar 

  47. Dawood S, Austin L, Cristofanilli M. Cancer stem cells: implications for cancer therapy. Oncology. 2014;28:1101–7.

    PubMed  Google Scholar 

  48. Toh TB, Lim JJ, Chow EK. Epigenetics in cancer stem cells. Mol Cancer. 2017;16:29.

    Article  PubMed  PubMed Central  Google Scholar 

  49. Nassar D, Blanpain C. Cancer stem cells: basic concepts and therapeutic implications. Annu Rev Pathol. 2016;23:47–76.

    Article  Google Scholar 

  50. Boussommier-Calleja A, Li R, Chen MB, Wong SC, Kamm RD. Microfluidics: a new tool for modeling cancer-immune interactions. Trends Cancer. 2016;2:6–19.

    Article  PubMed  PubMed Central  Google Scholar 

  51. Chaicharoenaudomrung N, Kunhorm P, Noisa P. Three-dimensional cell culture systems as an in vitro platform for cancer and stem cell modeling. World J Stem Cells. 2019;11:1065–83.

    Article  PubMed  PubMed Central  Google Scholar 

  52. Song HH, Park KM, Gerecht S. Hydrogels to model 3D in vitro microenvironment of tumor vascularization. Adv Drug Deliv Rev. 2014;79:19–29.

    Article  PubMed  Google Scholar 

  53. Levinger I, Ventura Y, Vago R. Life is three dimensional-as in vitro cancer cultures should be. Adv Cancer Res. 2014;121:383–414.

    Article  PubMed  CAS  Google Scholar 

  54. Shen CN, Goh KS, Huang CR, Chiang TC, Lee CY, Jeng YM, et al. Lymphatic vessel remodeling and invasion in pancreatic cancer progression. EBioMedicine. 2019;47:98–113.

    Article  PubMed  PubMed Central  Google Scholar 

  55. Iwai S, Kishimoto S, Amano Y, Nishiguchi A, Matsusaki M, Takeshita A, et al. Three-dimensional cultured tissue constructs that imitate human living tissue organization for analysis of tumor cell invasion. J Biomed Mater Res A. 2019;107:292–300.

    Article  PubMed  CAS  Google Scholar 

  56. Harper SJ, Bates DO. VEGF-A splicing: the key to anti-angiogenic therapeutics. Nat Rev Cancer. 2008;8:880–7.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  57. Abdelnour SA, Abd El-Hack ME, Khafaga AF, Arif M, Taha AE, Noreldin AE. Stress biomarkers and proteomics alteration to thermal stress in ruminants: a review. J Therm Biol. 2019;79:120–34.

    Article  PubMed  CAS  Google Scholar 

  58. Somero GN. The cellular stress response and temperature: function, regulation, and evolution. J Exp Zool A Ecol Integr Physiol. 2020;333:379–97.

    Article  PubMed  CAS  Google Scholar 

  59. Burtscher M, Gatterer H, Burtscher J, Mairbäurl H. Extreme terrestrial environments: life in thermal stress and hypoxia—a narrative review. Front Physiol. 2018;9:572.

    Article  PubMed  PubMed Central  Google Scholar 

  60. Chan CJ, Whyte G, Boyde L, Salbreux G, Guck J. Impact of heating on passive and active biomechanics of suspended cells. Interface Focus. 2014;4:20130069–80.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  61. Yao J, Liu B, Qin F. Rapid temperature jump by infrared diode laser irradiation for patch-clamp studies. Biophysical J. 2009;96:3611–9.

    Article  CAS  Google Scholar 

  62. Yao J, Liu B, Qin F. Modular thermal sensors in temperature-gated transient receptor potential (TRP) channels. Proc Natl Acad Sci USA. 2011;108:11109–14.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  63. Su T, Huang L, Zhang N, Peng S, Li X, Wei G, et al. FGF14 functions as a tumor suppressor through inhibiting PI3K/AKT/mTOR pathway in colorectal cancer. J Cancer 2020;11:819–25.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  64. Wang JX, Jia XJ, Liu Y, Dong JH, Ren XM, Xu O, et al. Silencing of miR-17-5p suppresses cell proliferation and promotes cell apoptosis by directly targeting PIK3R1 in laryngeal squamous cell carcinoma. Cancer Cell Int. 2020;20:14.

    Article  PubMed  PubMed Central  Google Scholar 

  65. Vasan N, Toska E, Scaltriti M. Overview of the relevance of PI3K pathway in HR-positive breast cancer. Ann Oncol. 2019;30(suppl 10):x3–x11.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  66. Shiozaki A, Kudou M, Ichikawa D, Fujiwara H, Shimizu H, Ishimoto T, et al. Esophageal cancer stem cells are suppressed by tranilast, a TRPV2 channel inhibitor. J Gastroenterol. 2018;53:197–207.

    Article  PubMed  CAS  Google Scholar 

  67. Lu YF, Yu JR, Yang Z, Zhu GX, Gao P, Wang H, et al. Promoter hypomethylation mediated upregulation of MicroRNA-10b-3p targets FOXO3 to promote the progression of esophageal squamous cell carcinoma (ESCC). J Exp Clin Cancer Res. 2018;37:301.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  68. Hong Y, Ding ZY. PD-1 inhibitors in the advanced esophageal cancer. Front Pharmacol. 2019;10:1418.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  69. Hirano H, Kato K. Systemic treatment of advanced esophageal squamous cell carcinoma: chemotherapy, molecular-targeting therapy and immunotherapy. Jpn J Clin Oncol. 2019;49:412–20.

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

We are grateful to Prof. GSW Tsao (Hong Kong University) for giving us the immortalised esophageal squamous cell line NE2 as a gift. We thank colleagues in GIBH, including Prof. Peng Li, Dr. Zhiwu Jiang for assistance in the establishment of GL-labelled cell lines, Dr. Kepin Wang, Dr. Jingke Xie for technical help with CRISPR–Cas9 editing and Prof. Liangxue Lai for giving us the Cas9-G418 plasmid. We thank prof. Huayu Qi for important comments on the manuscript.

Funding

This work was supported by Frontier Research Programs of Guangzhou Regenerative Medicine and Health Guangdong Laboratory (Grant Nos. 2018GZR110105020 and 2018GZR110105019), the National Natural Science Foundation of China (31671211) and the Science and Technology Planning Project of Guangdong Province, China (2017B030314056).

Author information

Authors and Affiliations

  1. CAS Key Laboratory of Regenerative Biology, Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China

    Rongqi Huang, Shuai Li, Jean de Dieu Habimana, Zuoxian Lin, Yuchen Yang, Na Cheng & Zhiyuan Li

  2. University of Chinese Academy of Sciences, Beijing, China

    Rongqi Huang, Shuai Li, Jean de Dieu Habimana & Zhiyuan Li

  3. School of Life Sciences, University of Science and Technology of China, Hefei, China

    Chao Tian, Huifang Zhao, Ling Wang & Zhiyuan Li

  4. Department of Anatomy and Neurobiology, Xiangya School of Medicine, Central South University, Changsha, China

    Peng Zhou, Wei Xie, Jie Xiao & Zhiyuan Li

  5. Department of Pathology, the Second Xiangya Hospital of Central South University, Changsha, China

    Peng Zhou

  6. Department of Hepatobiliary Surgery, Provincial Cancer Hospital of Hunan, Changsha, China

    Wei Xie

  7. Guangzhou Regenerative Medicine and Health Guangdong Laboratory, Guangzhou, China

    Zuoxian Lin, Yuchen Yang, Na Cheng & Zhiyuan Li

  8. GZMU-GIBH Joint School of Life Sciences, Guangzhou Medical University, Guangzhou, China

    Zhiyuan Li

Authors
  1. Rongqi Huang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Shuai Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Chao Tian
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Peng Zhou
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Huifang Zhao
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Wei Xie
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Jie Xiao
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Ling Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Jean de Dieu Habimana
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Zuoxian Lin
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Yuchen Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Na Cheng
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Zhiyuan Li
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Conception and design: Z Li and RH; development of methodology: RH, PZ, HZ and JX; acquisition of the data (provided animals, acquired and managed patients, provided facilities, etc.): PZ, WX, JX, Z Lin, and NC; analysis and interpretation of data (e.g., statistical analysis, biostatistics, computational analysis): RH, SL, CT, LW and YY; writing, review, and/or revision of the manuscript: RH, JdDH and Z Li; study supervision: Z Li; all authors reviewed and approved the final version of the manuscript.

Corresponding author

Correspondence to Zhiyuan Li.

Ethics declarations

Ethics approval and consent to participate

All of the animal studies were conducted under protocols approved by the guidelines of the Ethics Committee of Animal Experiments at GIBH (No. 2016015). For the use of clinical materials for this study, prior patient consent and approval from the Institutional Research Ethics Committee of the Cancer Hospital of Hunan Province (No. CHH-YJ-0317005) and the Second Affiliated Hospital of Xiangya Medical School of Central South University (No. XY-2-18179) were obtained.

Consent to publish

Not applicable.

Competing interests

The authors declare no competing interests.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Rights and permissions

Reprints and Permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Huang, R., Li, S., Tian, C. et al. Thermal stress involved in TRPV2 promotes tumorigenesis through the pathways of HSP70/27 and PI3K/Akt/mTOR in esophageal squamous cell carcinoma. Br J Cancer 127, 1424–1439 (2022). https://doi.org/10.1038/s41416-022-01896-2

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41416-022-01896-2

This article is cited by

Search

Advanced search

Quick links