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Expression of the PTEN/FOXO3a/PLZF signalling pathway in pancreatic cancer and its significance in tumourigenesis and progression

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Summary

Pancreatic cancer (PC) is one of the most lethal gastrointestinal malignancies. The PTEN/AKT signalling pathway is closely related to the tumourigenesis and progression of PC. The downstream effectors, FOXO3a, PLZF and VEGF, are reported to be involved in angiogenesis, lymph node metastasis and poor survival in PC. By using tissue microarrays and immunohistochemistry, we found, that PTEN, FOXO3a and PLZF expression was significantly decreased in PC specimens compared with that in chronic pancreatitis (CP) specimens, while VEGF expression was significantly increased. Furthermore, the expression of PTEN was positively correlated with that of FOXO3a and PLZF but negatively correlated with that of VEGF. Our results suggest that the PTEN/FOXO3a/PLZF signalling pathway may negatively regulate VEGF expression in PC. Through clinical analysis of 69 PC patients, PTEN, FOXO3a and PLZF expression was found to be significantly decreased in specimens from PC patients with lymph node metastasis and poor prognosis, while VEGF expression was significantly increased. Taken together, these reaults suggest that the PTEN/FOXO3a/PLZF signalling pathway may be capable of inhibiting growth and metastasis in PC by regulating VEGF-mediated angiogenesis, which requires further in vivo and in vitro studies and can potentially be a therapeutic target for PC.

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Acknowledgments

This work was supported by the Ningbo Natural Science Foundation (grant number 2016A610189).

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  1. Qiubo Zhang and Xuanna Li contributed equally to this work.

Authors and Affiliations

  1. Department of Gastroenterology, Ningbo Medical Center Lihuili Hospital, No. 57 Xingning Road, Yinzhou District, Ningbo, 315040, China

    Qiubo Zhang, Xiaoling Shen, Xianwen Dong, Yufei Song & Xuesong Zhang

  2. Department of Gastroenterology, Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University, No. 107, Yanjiang West Road, Yuexiu District, Guangzhou, 510120, China

    Xuanna Li, Yaqing Li, Shaojie Chen & Kaihong Huang

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Correspondence to Kaihong Huang.

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Conflict of interest

Qiubo Zhang declares that she has no conflict of interest. Xuanna Li declares that she has no conflict of interest. Yaqing Li declares that she has no conflict of interest. Shaojie Chen declares that she has no conflict of interest. Xiaoling Shen declares that she has no conflict of interest. Xianwen Dong declares that he has no conflict of interest. Yufei Song declares that she has no conflict of interest. Xuesong Zhang declares that he has no conflict of interest. Kaihong Huang declares that he has no conflict of interest.

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This study was performed under a protocol approved by the Hospital Research Ethics Committee of Sun Yat-Sen University.

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Zhang, Q., Li, X., Li, Y. et al. Expression of the PTEN/FOXO3a/PLZF signalling pathway in pancreatic cancer and its significance in tumourigenesis and progression. Invest New Drugs 38, 321–328 (2020). https://doi.org/10.1007/s10637-019-00791-7

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