HSP40 co-chaperone protein Tid1 suppresses metastasis of head and neck cancer by inhibiting Galectin-7-TCF3-MMP9 axis signaling.
HSP40 co-chaperone protein Tid1 suppresses metastasis of head and neck cancer by inhibiting Galectin-7-TCF3-MMP9 axis signaling.
复制标题
作者：
Chen YS;Chang CW;Tsay YG;Huang LY;Wu YC;Cheng LH;Yang CC;Wu CH;Teo WH;Hung KF;Huang CY;Lee TC;Lo JF
人肿瘤性成虫盘（Tid 1）是一种DnaJ共伴侣蛋白，被归类为肿瘤抑制因子。以前，我们证明了Tid 1降低了头颈部鳞状细胞癌（HNSCC）的恶性程度。然而，Tid 1介导的抗转移的分子细节仍然难以捉摸。方法：我们使用亲和层析和系统质谱鉴定Tid 1相互作用的客户蛋白。检测HNSCC患者组织中Tid 1的免疫组织化学染色，以评估Tid 1相互作用客户蛋白的表达谱与病理特征和预后之间的关联。Tid 1相互作用的客户端蛋白在转移中的作用在体外和体内都得到了验证。确定了Tid 1相互作用客户蛋白的相互作用伴侣和下游靶标。结果：首次发现Galectin-7是Tid 1相互作用的客户蛋白之一。在HNSCC患者中确定了Tid 1和Galectin-7之间的蛋白质表达谱的负相关性。低Tid 1和高Galectin-7表达预测HNSCC的总生存率较差。此外，Tid 1取消了Galectin-7的核转位，并抑制Galectin-7诱导的肿瘤发生和转移。角质形成细胞特异性Tid 1缺陷小鼠与4-硝基喹啉-1-氧化物（4 NQO）治疗表现出增加的半乳糖凝集素-7蛋白水平，并有一个穷人的生存率。Tid 1通过其N-连接的糖基化与半乳糖凝集素7相互作用，以促进Tid 1介导的半乳糖凝集素7的泛素化和蛋白酶体降解。此外，Galectin-7通过上调MMP-9表达增强TCF 3转录因子的转录活性，在促进肿瘤发生和转移进展中发挥关键作用。结论：总的来说，未来通过激活Tid 1表达或反向抑制半乳糖凝集素-7的致癌功能的治疗可能在靶向HNSCC进展方面表现出巨大的潜力。
Human tumorous imaginal disc (Tid1), a DnaJ co-chaperone protein, is classified as a tumor suppressor. Previously, we demonstrated that Tid1 reduces head and neck squamous cell carcinoma (HNSCC) malignancy. However, the molecular details of Tid1-mediated anti-metastasis remain elusive. Methods: We used affinity chromatography and systemic mass spectrometry to identify Tid1-interacting client proteins. Immunohistochemical staining of Tid1 in HNSCC patient tissues was examined to evaluate the association between the expression profile of Tid1-interacting client proteins with pathologic features and prognosis. The roles of Tid1-interacting client proteins in metastasis were validated both in vitro and in vivo. The interacting partner and downstream target of Tid1-interacting client protein were determined. Results: Herein, we first revealed that Galectin-7 was one of the Tid1-interacting client proteins. An inverse association of protein expression profile between Tid1 and Galectin-7 was determined in HNSCC patients. Low Tid1 and high Galectin-7 expression predicted poor overall survival in HNSCC. Furthermore, Tid1 abolished the nuclear translocation of Galectin-7 and suppressed Galectin-7-induced tumorigenesis and metastasis. Keratinocyte-specific Tid1-deficient mice with 4-nitroquinoline-1-oxide (4NQO) treatment exhibited increased protein levels of Galectin-7 and had a poor survival rate. Tid1 interacted with Galectin-7 through its N-linked glycosylation to promote Tid1-mediated ubiquitination and proteasomal degradation of Galectin-7. Additionally, Galectin-7 played a critical role in promoting tumorigenesis and metastatic progression by enhancing the transcriptional activity of TCF3 transcription factor through elevating MMP-9 expression. Conclusions: Overall, future treatments through activating Tid1 expression or inversely repressing the oncogenic function of Galectin-7 may exhibit great potential in targeting HNSCC progression.
登录
查看更多内容
影响因子：
11.2
作者：
Doçi CL;Mikelis CM;Lionakis MS;Molinolo AA;Gutkind JS
通讯作者：
Gutkind JS
影响因子：
8
作者：
Kopitz, J;André, S;Gabius, HJ
通讯作者：
Gabius, HJ
影响因子：
11.2
作者：
Demers, Melanie;Biron-Pain, Katherine;St-Pierre, Yves
通讯作者：
St-Pierre, Yves
影响因子：
4.8
作者：
Garcia, Jacinto;Lopez, Montserrat;Leon, Xavier
通讯作者：
Leon, Xavier
影响因子：
29.4
作者：
Inagaki, Yutaka;Higashi, Kiyoshi;Okazaki, Isao
通讯作者：
Okazaki, Isao