IRGM promotes melanoma cell survival through autophagy and is a promising prognostic biomarker for clinical application.
IRGM promotes melanoma cell survival through autophagy and is a promising prognostic biomarker for clinical application.
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IRGM 通过自噬促进黑色素瘤细胞存活，是一种有前景的临床应用预后生物标志物
DOI：
10.1016/j.omto.2020.12.005
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发表时间：
2021-03-26
期刊：
影响因子：
--
通讯作者：
Li R
中科院分区：
文献类型：
--
作者：
Tian L;Meng H;Dong X;Li X;Shi Z;Li H;Zhang L;Yang Y;Liu R;Pei C;Li B;Xu H;Li R
先前，我们发现小鼠免疫相关的鸟苷三磷酸酶（GTdR）家族M蛋白1（Irgm 1）通过诱导细胞自噬通量和转移促进恶性黑色素瘤进展。人IRGM是一种功能上不同于其小鼠对应物的截短蛋白，具有几种剪接异构体。在本研究中，我们分析了IRGM与人黑色素瘤临床预后的关系，并研究了IRGM在人黑色素瘤细胞中的功能。来自训练队列（n = 144）的数据显示，IRGM的过表达与人组织芯片中的黑色素瘤发生和临床分期成比例。一项验证队列（n = 78）进一步证实，IRGM是促进黑色素瘤进展的独立风险因素，并与患者的生存率差相关。在IRGM亚型中，我们发现IRGMb负责这种相关性。此外，IRGM促进黑色素瘤细胞的生存，通过自噬，在体外和体内。我们进一步表明，阻断高迁移率族蛋白1（HMGB 1）从细胞核到细胞质的易位抑制了IRGM 1介导的细胞自噬并降低了细胞存活率。IRGM通过自噬作为黑色素瘤进展的正调节剂发挥作用，并可作为有希望的预后标志物和治疗靶点。黑色素瘤中人IRGM过表达与更晚期的临床分期、更强的转移和较差的存活率相关。IRGM结合HMGB-1通过增加自噬增强黑色素瘤细胞存活。我们的观察支持IRGM作为黑色素瘤预后标志物和潜在治疗靶点的实用性。
Previously, we showed that mouse immunity-related guanosine triphosphatase (GTPase) family M protein 1 (Irgm1) promotes malignant melanoma progression by inducing cellular autophagy flux and metastasis. Human IRGM, a truncated protein functionally distinct from its mouse counterpart, has several splice isoforms. In this study, we analyzed the association of IRGM and human melanoma clinical prognosis and investigated the function of IRGM in human melanoma cells. Data from the training cohort (n = 144) showed that overexpression of IRGM is proportional to melanoma genesis and clinical stages in human tissue chips. A validation cohort (n = 78) further confirmed that IRGM is an independent risk factor promoting melanoma progression and is associated with poor survival of patients. Among IRGM isoforms, we found that IRGMb is responsible for such correlation. In addition, IRGM promoted melanoma cell survival through autophagy, both in vitro and in vivo. We further showed that the blockade of translocation of high-mobility group box 1 (HMGB1) from the nucleus to cytoplasm inhibits IRGM1-mediated cellular autophagy and reduces cell survival. IRGM functions as a positive regulator of melanoma progression through autophagy and may serve as a promising prognostic marker and therapeutic target. Human IRGM overexpression in melanoma is associated with more advanced clinical stages, stronger metastasis, and poor survival. IRGM coupled with HMGB-1 enhanced melanoma cell survival through increasing autophagy. Our observations support utility of IRGM as a prognostic marker and potential therapeutic target for melanoma.
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卵子黑色素瘤：从诊断到治疗以及两者之间的科学。
影响因子：
6.2
作者：
Chattopadhyay C;Kim DW;Gombos DS;Oba J;Qin Y;Williams MD;Esmaeli B;Grimm EA;Wargo JA;Woodman SE;Patel SP
通讯作者：
Patel SP
影响因子：
11.2
作者：
Gewirtz DA
通讯作者：
Gewirtz DA
DOI：
10.1093/jnci/djn290
发表时间：
2008-09-17
期刊：
JOURNAL OF THE NATIONAL CANCER INSTITUTE
影响因子：
--
作者：
Leu, Monica;Reilly, Marie;Czene, Kamila
通讯作者：
Czene, Kamila
影响因子：
16
作者：
Mehto, Subhash;Jena, Kautilya Kumar;Chauhan, Santosh
通讯作者：
Chauhan, Santosh
影响因子：
30.8
作者：
McCarroll, Steven A.;Huett, Alan;Kuballa, Petric;Chilewski, Shannon D.;Landry, Aimee;Goyette, Philippe;Zody, Michael C.;Hall, Jennifer L.;Brant, Steven R.;Cho, Judy H.;Duerr, Richard H.;Silverberg, Mark S.;Taylor, Kent D.;Rioux, John D.;Altshuler, David;Daly, Mark J.;Xavier, Ramnik J.
通讯作者：
Xavier, Ramnik J.