Abstract
Lung cancer is the most common malignancy and the leading cause of cancer death worldwide, and lung adenocarcinoma (LUAD) is the most prevalent subtype. Considering the emergence of resistance to therapies, it is urgent to develop more effective therapies to improve the prognosis. Here we reported that pancreatic progenitor cell differentiation and proliferation factor (PPDPF) deficiency inhibited LUAD development both in vitro and in vivo. Mechanistically, PPDPF induces hyperactive STAT3 by interfering STAT3-PTPN1 interaction. Activated STAT3 promoted BMPR2 transcription, which further inhibited apoptosis. Moreover, PPDPF reduced NK cell infiltration and activation to develop an immunosuppressive microenvironment, which was also mediated by STAT3. Furthermore, we identified that the expression of PPDPF was positively correlated with the malignant features of LUAD, as well as BMPR2 and p-STAT3 level in clinical samples. Therefore, our study suggests that PPDPF positively regulates BMPR2 expression and facilitates immune escape via regulating STAT3 activity, providing a potential therapy target for LUAD.
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Data availability
All data supporting the findings of this study are provided within the paper and its Supplementary information. All additional information will be made available upon reasonable request to the authors. Source data are provided with this paper.
Change history
25 July 2023
A Correction to this paper has been published: https://doi.org/10.1038/s41388-023-02735-1
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Acknowledgements
The authors thank the New World Group for their Charitable Foundation to establish the Institute for Nutritional Sciences, SIBS, CAS-New World Joint Laboratory, which have given full support to this study.
Funding
This work was supported by the National Natural Science Foundation of China (82172950, 81972757), Youth Innovation Promotion Association of Chinese Academy of Sciences grant (2017324) and Sanofi-SIBS 2018 Young Faculty Award to J-JL; and the National Natural Science Foundation of China (81730083 and 82030084) to DX.
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Conceptualization: Q-WZ, DX and J-JL; Data curation, Q-WZ, DX and J-JL; Funding acquisition, DX and J-JL; Methodology, Q-WZ, Q-ZN, BZ, XL, NM, Y-KW, SX, H-JC, JX, F-KZ, E-BZ, X-SQ, X-FD and Z-GL; Technical assistance in the flow cytometry, LQ; Patient samples collecting, X-LZ, X-LZ and Z-HD; Project administration, X-LZ, DX and J-JL; Writing—original draft, Q-WZ; Writing—review & editing, DX and J-JL. All authors have read and agreed to the published version of the manuscript.
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Zheng, QW., Ni, QZ., Zhu, B. et al. PPDPF promotes lung adenocarcinoma progression via inhibiting apoptosis and NK cell-mediated cytotoxicity through STAT3. Oncogene 41, 4244–4256 (2022). https://doi.org/10.1038/s41388-022-02418-3
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DOI: https://doi.org/10.1038/s41388-022-02418-3