HMGA1, Moonlighting Protein Function, and Cellular Real Estate: Location, Location, Location!
HMGA1, Moonlighting Protein Function, and Cellular Real Estate: Location, Location, Location!
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DOI：
10.3390/biom11091334
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发表时间：
2021-09-09
期刊：
影响因子：
5.5
通讯作者：
Villanueva J
中科院分区：
文献类型：
--
作者：
Pujals M;Resar L;Villanueva J
编码高迁移率族A1（HMGA 1）染色质重塑蛋白的基因在多种癌症中上调，高水平预示着不良的临床结果。直到最近，HMGA 1被认为是一种核蛋白，通过转录调节基因表达和下游信号通路在癌症中发挥作用。然而，在侵袭性三阴性乳腺癌（TNBC）细胞系中发现细胞外HMGA 1-β自分泌环暗示HMGA 1是具有取决于细胞位置的不同功能的“兼职蛋白”。在这里，我们回顾了HMGA 1的作用，不仅作为癌症和干细胞中的染色质调节因子，而且作为驱动肿瘤进展的潜在分泌因子。先前的工作发现，HMGA 1是从TNBC细胞系分泌的，在那里它通过晚期糖基化终末产物（AGEs）受体发出信号，以促进参与肿瘤侵袭和转移进展的表型。原发性TNBC肿瘤的研究还表明，HMGA 1分泌与TNBC的远处转移有关。鉴于靶向细胞外蛋白的治疗潜力，有必要进一步开展工作以确认这种作用在其他情况下。事实上，核和分泌的HMGA 1之间的串扰可能会改变我们对肿瘤发展的理解，并揭示与过表达HMGA 1的各种人类癌症相关的新治疗机会。
The gene encoding the High Mobility Group A1 (HMGA1) chromatin remodeling protein is upregulated in diverse cancers where high levels portend adverse clinical outcomes. Until recently, HMGA1 was assumed to be a nuclear protein exerting its role in cancer by transcriptionally modulating gene expression and downstream signaling pathways. However, the discovery of an extracellular HMGA1-RAGE autocrine loop in invasive triple-negative breast cancer (TNBC) cell lines implicates HMGA1 as a “moonlighting protein” with different functions depending upon cellular location. Here, we review the role of HMGA1, not only as a chromatin regulator in cancer and stem cells, but also as a potential secreted factor that drives tumor progression. Prior work found that HMGA1 is secreted from TNBC cell lines where it signals through the receptor for advanced glycation end products (RAGE) to foster phenotypes involved in tumor invasion and metastatic progression. Studies in primary TNBC tumors also suggest that HMGA1 secretion associates with distant metastasis in TNBC. Given the therapeutic potential to target extracellular proteins, further work to confirm this role in other contexts is warranted. Indeed, crosstalk between nuclear and secreted HMGA1 could change our understanding of tumor development and reveal novel therapeutic opportunities relevant to diverse human cancers overexpressing HMGA1.
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曼氏菌HMGB1蛋白的CK2磷酸化调节其细胞流量和分泌，但不能调节其DNA交易。
影响因子：
3.7
作者：
de Abreu da Silva IC;Carneiro VC;Maciel Rde M;da Costa RF;Furtado DR;de Oliveira FM;da Silva-Neto MA;Rumjanek FD;Fantappié MR
通讯作者：
Fantappié MR
影响因子：
--
作者：
Cabral, Matthew;Anjard, Christophe;Kuspa, Adam
通讯作者：
Kuspa, Adam
DOI：
10.1083/jcb.201704056
发表时间：
2017-09-04
期刊：
The Journal of cell biology
影响因子：
--
作者：
Cruz-Garcia D;Brouwers N;Duran JM;Mora G;Curwin AJ;Malhotra V
通讯作者：
Malhotra V
影响因子：
4.6
作者：
Chen YC;Statt S;Wu R;Chang HT;Liao JW;Wang CN;Shyu WC;Lee CC
通讯作者：
Lee CC
影响因子：
8
作者：
Body-Malapel, M.;Djouina, M.;Vignal, C.
通讯作者：
Vignal, C.