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NETO2 promotes melanoma progression via activation of the Ca2+/CaMKII signaling pathway

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Abstract

Melanoma is the most aggressive cutaneous tumor. Neuropilin and tolloid-like 2 (NETO2) is closely related to tumorigenesis. However, the functional significance of NETO2 in melanoma progression remains unclear. Herein, we found that NETO2 expression was augmented in melanoma clinical tissues and associated with poor prognosis in melanoma patients. Disrupting NETO2 expression markedly inhibited melanoma proliferation, malignant growth, migration, and invasion by downregulating the levels of calcium ions (Ca2+) and the expression of key genes involved in the calcium signaling pathway. By contrast, NETO2 overexpression had the opposite effects. Importantly, pharmacological inhibition of CaMKII/CREB activity with the CaMKII inhibitor KN93 suppressed NETO2-induced proliferation and melanoma metastasis. Overall, this study uncovered the crucial role of NETO2-mediated regulation in melanoma progression, indicating that targeting NETO2 may effectively improve melanoma treatment.

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Acknowledgements

This study was supported by the National Natural Science Foundation of China (Nos. 82073458, 82173424, 81773341, 81772917, and 81830096). This research also was supported by the Science and Technology Innovation Program of Hunan Province (No. 2021RC4013) and the Program of Introducing Talents of Discipline to Universities (111 Project, No. B20017)

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Authors and Affiliations

  1. Department of Dermatology, Xiangya Hospital, Central South University, Changsha, 41000, China

    Susi Zhu, Xu Zhang, Yeye Guo, Ling Tang, Zhe Zhou, Xiang Chen & Cong Peng

  2. Hunan Key Laboratory of Skin Cancer and Psoriasis, Changsha, 41000, China

    Susi Zhu, Xu Zhang, Yeye Guo, Ling Tang, Zhe Zhou, Xiang Chen & Cong Peng

  3. Hunan Engineering Research Center of Skin Health and Disease, Changsha, 41000, China

    Susi Zhu, Xu Zhang, Yeye Guo, Ling Tang, Zhe Zhou, Xiang Chen & Cong Peng

  4. National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, 41000, China

    Susi Zhu, Xu Zhang, Yeye Guo, Ling Tang, Zhe Zhou, Xiang Chen & Cong Peng

  5. Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, 41000, China

    Susi Zhu & Ling Tang

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  1. Susi Zhu
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  2. Xu Zhang
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Correspondence to Xiang Chen or Cong Peng.

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Susi Zhu, Xu Zhang, Yeye Guo, Ling Tang, Zhe Zhou, Xiang Chen, and Cong Peng declare that they have no competing interests. All institutional and national guidelines for the care and use of laboratory animals were followed.

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Zhu, S., Zhang, X., Guo, Y. et al. NETO2 promotes melanoma progression via activation of the Ca2+/CaMKII signaling pathway. Front. Med. 17, 263–274 (2023). https://doi.org/10.1007/s11684-022-0935-0

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  • DOI: https://doi.org/10.1007/s11684-022-0935-0

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