Open Access

VNN1 overexpression in pancreatic cancer cells inhibits paraneoplastic islet function by increasing oxidative stress and inducing β‑cell dedifferentiation

  • Authors:
    • Wenjie Qin
    • Muxing Kang
    • Chao Li
    • Wen Zheng
    • Qingqu Guo
  • View Affiliations

  • Published online on: April 27, 2023     https://doi.org/10.3892/or.2023.8557
  • Article Number: 120
  • Copyright: © Qin et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Vanin‑1 (VNN1) may be a potential biomarker for the early screening of pancreatic cancer (PC)‑associated diabetes (PCAD). A previous study by the authors reported that cysteamine secreted by VNN1‑overexpressing PC cells induced the dysfunction of paraneoplastic insulinoma cell lines by increasing oxidative stress. In the present study, it was observed that both cysteamine and exosomes (Exos) secreted by VNN1‑overexpressing PC cells aggravated the dysfunction of mouse primary islets. PC‑derived VNN1 could be transported into islets through PC cell‑derived Exos (PC‑Exos). However, β‑cell dedifferentiation, and not cysteamine‑mediated oxidative stress, was responsible for the islet dysfunction induced by VNN1‑containing Exos. VNN1 inhibited the phosphorylation of AMPK and GAPDH, and prevented Sirt1 activation and FoxO1 deacetylation in islets, which may be responsible for the induction of β‑cell dedifferentiation induced by VNN1‑overexpressing PC‑Exos. Furthermore, it was demonstrated that VNN1‑overexpressing PC cells further impaired the functions of paraneoplastic islets in vivo using diabetic mice with islets transplanted under the kidney capsule. On the whole, the present study demonstrates that PC cells overexpressing VNN1 exacerbate the dysfunction of paraneoplastic islets by inducing oxidative stress and β‑cell dedifferentiation.
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June-2023
Volume 49 Issue 6

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Spandidos Publications style
Qin W, Kang M, Li C, Zheng W and Guo Q: VNN1 overexpression in pancreatic cancer cells inhibits paraneoplastic islet function by increasing oxidative stress and inducing β‑cell dedifferentiation. Oncol Rep 49: 120, 2023.
APA
Qin, W., Kang, M., Li, C., Zheng, W., & Guo, Q. (2023). VNN1 overexpression in pancreatic cancer cells inhibits paraneoplastic islet function by increasing oxidative stress and inducing β‑cell dedifferentiation. Oncology Reports, 49, 120. https://doi.org/10.3892/or.2023.8557
MLA
Qin, W., Kang, M., Li, C., Zheng, W., Guo, Q."VNN1 overexpression in pancreatic cancer cells inhibits paraneoplastic islet function by increasing oxidative stress and inducing β‑cell dedifferentiation". Oncology Reports 49.6 (2023): 120.
Chicago
Qin, W., Kang, M., Li, C., Zheng, W., Guo, Q."VNN1 overexpression in pancreatic cancer cells inhibits paraneoplastic islet function by increasing oxidative stress and inducing β‑cell dedifferentiation". Oncology Reports 49, no. 6 (2023): 120. https://doi.org/10.3892/or.2023.8557