RARRES3 suppresses breast cancer lung metastasis by regulating adhesion and differentiation.
RARRES3 suppresses breast cancer lung metastasis by regulating adhesion and differentiation.
复制标题
RARRES3通过调节粘附和分化来抑制乳腺癌肺转移。
DOI：
10.15252/emmm.201303675
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发表时间：
2014-07
影响因子：
11.1
通讯作者：
Gomis RR
中科院分区：
文献类型：
--
作者：
Morales M;Arenas EJ;Urosevic J;Guiu M;Fernández E;Planet E;Fenwick RB;Fernández-Ruiz S;Salvatella X;Reverter D;Carracedo A;Massagué J;Gomis RR
在雌激素受体阴性的乳腺癌患者中，转移性复发通常发生在肺中，并导致疾病的致命结局。因此，需要更好地了解转移的生物学。特别是，识别有肺转移风险的患者的生物标志物可以为新的治疗机会开辟道路。在这里，我们描述了RARRES 3的生物活性，RARRES 3是一种新的转移抑制基因，其在原发性乳腺肿瘤中的表达减少，确定了一个更有可能发生肺转移的患者亚组。我们发现，RARRES 3下调通过促进肿瘤细胞粘附到肺实质来启动转移的能力。此外，由于RARRES 3磷脂酶A1/A2活性的丧失而导致的肿瘤细胞分化受损也有助于肺转移。我们的研究结果确立了RARRES 3下调作为一种潜在的生物标志物，用于识别可能从辅助治疗中的分化治疗中获益的肺转移高风险患者。
In estrogen receptor-negative breast cancer patients, metastatic relapse usually occurs in the lung and is responsible for the fatal outcome of the disease. Thus, a better understanding of the biology of metastasis is needed. In particular, biomarkers to identify patients that are at risk of lung metastasis could open the avenue for new therapeutic opportunities. Here we characterize the biological activity of RARRES3, a new metastasis suppressor gene whose reduced expression in the primary breast tumors identifies a subgroup of patients more likely to develop lung metastasis. We show that RARRES3 downregulation engages metastasis-initiating capabilities by facilitating adhesion of the tumor cells to the lung parenchyma. In addition, impaired tumor cell differentiation due to the loss of RARRES3 phospholipase A1/A2 activity also contributes to lung metastasis. Our results establish RARRES3 downregulation as a potential biomarker to identify patients at high risk of lung metastasis who might benefit from a differentiation treatment in the adjuvant programme.