【佳学基因检测】ATRX 的缺失促进骨肉瘤的侵袭性特征，增加 NF-κB 信号传导和整合素结合

夫妻备孕基因检测项目要点

体会记录《JCI Insight》在. 2022 Sep 8;7(17):e151583.发表了一篇题目为《ATRX 的缺失促进骨肉瘤的侵袭性特征，增加 NF-κB 信号传导和整合素结合》肿瘤靶向药物治疗基因检测临床研究文章。该研究由Suzanne Bartholf DeWitt, Sarah Hoskinson Plumlee, Hailey E Brighton, Dharshan Sivaraj, E J Martz, Maryam Zand, Vardhman Kumar, Maya U Sheth, Warren Floyd, Jacob V Spruance, Nathan Hawkey, Shyni Varghese, Jianhua Ruan, David G Kirsch, Jason A Somarelli, Ben Alman, William C Eward等完成。促进了肿瘤的精准治疗与个性化用药的发展，进一步强调了基因信息检测与分析的重要性。

肿瘤靶向药物及精准治疗临床研究内容关键词：

细胞迁移/粘附,细胞外基质,整合素,肿瘤学

肿瘤靶向治疗基因检测临床应用结果

骨肉瘤 (总生存期) 是一种致命的疾病，很少有已知的靶向疗法。在这里，我们表明降低的 ATRX 表达与更具侵袭性的肿瘤细胞表型相关，包括增加的生长、迁移、侵袭和转移。这些表型变化与 NF-κB 信号传导、细胞外基质重塑、整合素 αvβ3 表达增加和 ETS 家族转录因子结合的激活相对应。在这里，我们在体外、体内和人类 总生存期 患者的数据集中描述了这些变化。这种增加的攻击性实质上使 ATRX 缺陷的 总生存期 细胞对整合素信号传导抑制敏感。因此，ATRX 在 总生存期 中发挥重要的肿瘤抑制作用，该基因功能的丧失可能是新的治疗漏洞的基础。 ATRX 表达与整合素结合、NF-κB 激活和 ETS 家族转录因子结合之间的关系在先前的研究中没有描述，并且可能影响其他 ATRX 缺失疾病的病理生理学，包括其他癌症和 ATR-X α 地中海贫血残疾综合征。关键词：细胞迁移/粘附；细胞外基质；整合素；肿瘤学。

肿瘤发生与复发转移国际数据库描述：

Osteosarcoma (OS) is a lethal disease with few known targeted therapies. Here, we show that decreased ATRX expression is associated with more aggressive tumor cell phenotypes, including increased growth, migration, invasion, and metastasis. These phenotypic changes correspond with activation of NF-κB signaling, extracellular matrix remodeling, increased integrin αvβ3 expression, and ETS family transcription factor binding. Here, we characterize these changes in vitro, in vivo, and in a data set of human OS patients. This increased aggression substantially sensitizes ATRX-deficient OS cells to integrin signaling inhibition. Thus, ATRX plays an important tumor-suppression role in OS, and loss of function of this gene may underlie new therapeutic vulnerabilities. The relationship between ATRX expression and integrin binding, NF-κB activation, and ETS family transcription factor binding has not been described in previous studies and may impact the pathophysiology of other diseases with ATRX loss, including other cancers and the ATR-X α thalassemia intellectual disability syndrome.Keywords: Cell migration/adhesion; Extracellular matrix; Integrins; Oncology.