Kinoshita Juri, Kinoshita Yuriko, Nomura Tadashi, Inoue Yoshihiro H
Biomedical Research Center, Kyoto Institute of Technology, Matsugasaki, Sakyo, Kyoto 606-0962, Japan.
Graduate School of Science and Technology, Kyoto Institute of Technology, Matsugasaki, Sakyo, Kyoto 606-8585, Japan.
Int J Mol Sci. 2024 Dec 6;25(23):13110. doi: 10.3390/ijms252313110.
Turandot (Tot) family proteins, which are induced via the JAK/STAT pathway after infection, also suppress lymph gland tumors in mutant larvae. We investigated the potential role of hemocytes in induction in tumor-bearing mutants via immunostaining and RNAi experiments. Normal hemocytes transplanted into mutant larvae were recruited to the tumor and fat body (FB), suggesting that these cells transmit tumor-related information. The transplanted hemocytes ectopically expressed Unpaired3 (Upd3), which is necessary for the activation of JAK/STAT. Eiger, a tumor necrosis factor (TNF) ortholog, was highly expressed in tumors. Depletion of the Eiger receptor in hemocytes reduced levels and eventually enhanced tumor growth. The c-Jun N-terminal kinase (JNK) pathway, acting downstream of the receptor, was also activated in the hemocytes of mutants. Downregulation of the JNK pathway in hemocytes inhibited induction, leading to enhanced tumor growth. These results suggest that expression in hemocytes depends on the Eiger-JNK pathway. We propose that after Eiger activates the JNK pathway in hemocytes present on the tumor, cells expressing Upd3 are recruited to the FB. Upd3 then activates JAK/STAT to induce the expression of antitumor proteins. This study highlights the intricate communication between tissues via blood cells during tumor suppression.
图兰朵（Tot）家族蛋白在感染后通过JAK/STAT途径被诱导产生，它也能抑制突变幼虫中的淋巴腺肿瘤。我们通过免疫染色和RNA干扰实验研究了血细胞在荷瘤突变体诱导过程中的潜在作用。移植到突变幼虫体内的正常血细胞会被募集到肿瘤和脂肪体（FB）中，这表明这些细胞传递与肿瘤相关的信息。移植的血细胞异位表达了无翅型基因3（Upd3），这是激活JAK/STAT所必需的。艾格（Eiger），一种肿瘤坏死因子（TNF）直系同源物，在肿瘤中高度表达。血细胞中艾格受体的缺失降低了其水平，并最终促进了肿瘤生长。在受体下游起作用的c-Jun氨基末端激酶（JNK）途径，在突变体的血细胞中也被激活。血细胞中JNK途径的下调抑制了其诱导作用，导致肿瘤生长增强。这些结果表明，血细胞中的表达依赖于艾格-JNK途径。我们提出，在艾格激活肿瘤上存在的血细胞中的JNK途径后，表达Upd3的细胞被募集到脂肪体。然后Upd3激活JAK/STAT以诱导抗肿瘤蛋白的表达。这项研究突出了肿瘤抑制过程中组织间通过血细胞进行的复杂通讯。
