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. 2023 Apr;17(2):263-274.
doi: 10.1007/s11684-022-0935-0. Epub 2023 Feb 4.

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

Susi Zhu  1   2   3   4   5 , Xu Zhang  1   2   3   4 , Yeye Guo  1   2   3   4 , Ling Tang  1   2   3   4   5 , Zhe Zhou  1   2   3   4 , Xiang Chen  6   7   8   9 , Cong Peng  10   11   12   13
Affiliations

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

Susi Zhu et al. Front Med. 2023 Apr.

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.

Keywords: Ca2+/CaMKII signaling pathway; melanoma; neuropilin and tolloid-like 2.

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