Iron accelerates Fusobacterium nucleatum-induced CCL8 expression in macrophages and is associated with colorectal cancer progression.
Iron accelerates Fusobacterium nucleatum-induced CCL8 expression in macrophages and is associated with colorectal cancer progression.
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DOI：
10.1172/jci.insight.156802
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发表时间：
2022-11-08
期刊：
影响因子：
8
通讯作者：
Moroishi, Toshiro
中科院分区：
文献类型：
--
作者：
Yamane, Taishi;Kanamori, Yohei;Sawayama, Hiroshi;Yano, Hiromu;Nita, Akihiro;Ohta, Yudai;Hinokuma, Hironori;Maeda, Ayato;Iwai, Akiko;Matsumoto, Takashi;Shimoda, Mayuko;Niimura, Mayumi;Usuki, Shingo;Yasuda-Yoshihara, Noriko;Niwa, Masato;Baba, Yoshifumi;Ishimoto, Takatsugu;Komohara, Yoshihiro;Sawa, Tomohiro;Hirayama, Tasuku;Baba, Hideo;Moroishi, Toshiro
越来越多的证据表明，结直肠肿瘤组织中高水平的具核梭杆菌可能与结直肠癌（CRC）患者的不良预后相关;然而，关于F.核阳性CRC仍然有限。在此，我们证明高铁状态与F。核质血清转铁蛋白饱和度升高的CRC患者在肿瘤微环境中的巨噬细胞中表现出优先的铁沉积。此外，F. Nucleatum通过TLR 4/NF-κB信号通路诱导巨噬细胞表达CCL 8，而缺铁则抑制CCL 8的表达。机制上，铁通过激活丝氨酸/苏氨酸磷酸酶减弱NF-κB p65的抑制性磷酸化，增加巨噬细胞中促肿瘤趋化因子的产生。我们的观察表明铁在调节NF-κB信号通路中起关键作用，并提示其作为F.核阳性CRC。
Accumulating evidence suggests that high levels of Fusobacterium nucleatum in colorectal tumor tissues can be associated with poor prognosis in patients with colorectal cancer (CRC); however, data regarding distinct prognostic subgroups in F. nucleatum–positive CRC remain limited. Herein, we demonstrate that high-iron status was associated with a worse prognosis in patients with CRC with F. nucleatum. Patients with CRC presenting elevated serum transferrin saturation exhibited preferential iron deposition in macrophages in the tumor microenvironment. In addition, F. nucleatum induced CCL8 expression in macrophages via the TLR4/NF-κB signaling pathway, which was inhibited by iron deficiency. Mechanistically, iron attenuated the inhibitory phosphorylation of NF-κB p65 by activating serine/threonine phosphatases, augmenting tumor-promoting chemokine production in macrophages. Our observations indicate a key role for iron in modulating the NF-κB signaling pathway and suggest its prognostic potential as a determining factor for interpatient heterogeneity in F. nucleatum–positive CRC.
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影响因子：
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