NOX5 mediates the crosstalk between tumor cells and cancer-associated fibroblasts via regulating cytokine network.
NOX5 mediates the crosstalk between tumor cells and cancer-associated fibroblasts via regulating cytokine network.
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NOX5通过调节细胞因子网络介导肿瘤细胞和癌症相关成纤维细胞之间的串扰
DOI：
10.1002/ctm2.472
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发表时间：
2021-08
影响因子：
10.6
通讯作者：
Zhan Q
中科院分区：
文献类型：
--
作者：
Chen J;Wang Y;Zhang W;Zhao D;Zhang L;Zhang J;Fan J;Zhan Q
癌症相关成纤维细胞（CAF）的激活是肿瘤恶性肿瘤的一个重要特征。肿瘤细胞和CAF之间的相互作用不仅促进肿瘤的进展和转移，而且维持CAF的促肿瘤功能。然而，肿瘤细胞如何轻松适应这些功能性 CAF 仍不清楚。 NADPH 氧化酶 5 (NOX5) 是一种强活性氧产生剂，在食管鳞状细胞癌 (ESCC) 细胞中过度表达。在这项研究中，我们发现NOX5阳性ESCC细胞诱导正常成纤维细胞（NF）或脂肪源性间充质干细胞（MSC）表达CAFs-α平滑肌肌动蛋白标记物。此外，这些肿瘤细胞重新编程了激活的CAF的细胞因子谱，进一步刺激NF或MSC转化为CAF并诱导淋巴管生成，从而促进ESCC恶性肿瘤。 NOX5 激活肿瘤内 Src/核因子-κB 信号传导，刺激肿瘤细胞分泌肿瘤坏死因子-α (TNF-α)、白细胞介素-1β (IL-1β) 和乳酸。随后，TNF-α、IL-1β和乳酸激活CAF，并促进CAF分泌IL-6、IL-7、IL-8、CCL5和转化生长因子-β1。这些 CAF 衍生的细胞因子相互诱导 NOX5 阳性 ESCC 细胞的进展。我们的研究结果共同表明，NOX5 作为驱动癌蛋白，提供有利于肿瘤恶性进展的利基。 1. NOX5 控制的信号/细胞因子环介导 ESCC 和间质之间的串扰 2. NOX5 激活 Src/NF-κB 信号传导以促进 ESCC 细胞分泌 TNF-α、IL-1β 和乳酸，这些物质诱导 NF 和脂肪源性 MSC 活化成 CAF 3. 活化的 CAF 分泌 IL-6、IL-7、IL-8、CCL5 和 TGF-β1相互促进NOX5阳性ESCC细胞的恶性进展。
Activation of cancer‐associated fibroblasts (CAFs) is a crucial feature for tumor malignancy. The reciprocal interplay between tumor cells and CAFs not only facilitates tumor progression and metastasis but also sustains the tumor‐promoting function of CAFs. Nevertheless, how tumor cells readily adapt to these functional CAFs is still unclear. NADPH oxidase 5 (NOX5) is a strong reactive oxygen species producer overexpressed in esophageal squamous cell carcinoma (ESCC) cells. In this study, we showed that NOX5‐positive ESCC cells induced normal fibroblasts (NFs) or adipose‐derived mesenchymal stem cells (MSCs) to express the marker of CAFs‐α smooth muscle actin. Moreover, these tumor cells reprogrammed the cytokine profile of the activated CAFs, which further stimulated NFs or MSCs to CAFs and induced lymphangiogenesis to facilitate ESCC malignancy. NOX5 activated intratumoral Src/nuclear factor‐κB signaling to stimulate secretion of tumor necrosis factor‐α (TNF‐α), interleukin‐1β (IL‐1β), and lactate from tumor cells. Subsequently, TNF‐α, IL‐1β, and lactate activated CAFs, and facilitated the secretion of IL‐6, IL‐7, IL‐8, CCL5, and transforming growth factor‐β1 from CAFs. These CAFs‐derived cytokines reciprocally induced the progression of NOX5‐positive ESCC cells. Our findings together indicate that NOX5 serves as the driving oncoprotein to provide a niche that is beneficial for tumor malignant progression. 1. NOX5‐controlled signaling/cytokine loop mediates crosstalk between ESCC and stroma 2. NOX5 activates Src/NF‐κB signaling to facilitate secretion of TNF‐α, IL‐1β and lactate from ESCC cells, and these substances induce the activation of NFs and adipose‐derived MSCs into CAFs 3. IL‐6, IL‐7, IL‐8, CCL5, and TGF‐β1 secreted from activated‐CAFs reciprocally promote the malignant progression of NOX5‐positive ESCC cells.
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DOI：
10.1186/s13058-016-0740-2
发表时间：
2016-08-11
期刊：
Breast cancer research : BCR
影响因子：
--
作者：
Bussard KM;Mutkus L;Stumpf K;Gomez-Manzano C;Marini FC
通讯作者：
Marini FC
影响因子：
10.5
作者：
Chien, Yuchen;Scuoppo, Claudio;Lowe, Scott W.
通讯作者：
Lowe, Scott W.
影响因子：
7
作者：
Cheteh, Emarndeena H.;Sarne, Victoria;Wiman, Klas G.
通讯作者：
Wiman, Klas G.
影响因子：
3.8
作者：
Goulet, Cassandra Ringuette;Champagne, Audrey;Bolduc, Stephane
通讯作者：
Bolduc, Stephane
癌症相关成纤维细胞通过旁分泌信号调节肺癌干细胞的可塑性
影响因子：
16.6
作者：
Chen, Wan-Jiun;Ho, Chao-Chi;Yang, Pan-Chyr
通讯作者：
Yang, Pan-Chyr