JBC：NOG基因促进乳腺癌细胞骨转移

乳腺癌细胞经常从肿瘤原位组织侵入骨骼，导致病人的生存机会减少。这个转移过程是非常复杂的，乳腺癌细胞本身和骨环境等在这一过程中都发挥重要作用。近日，一项发表在Journal of Biological Chemistry杂志上的由西班牙生物医学研究所的研究人员完成的一项研究分析了乳腺癌细胞移植到骨的具体机制。

研究人员重点研究了骨骼发育中发挥重要作用的基因NOG。此前，NOG与前列腺癌骨转移的关联已有所研究，但其在乳腺癌骨转移中的具体作用仍不清楚。

Gomis和同事们研究发现，一旦乳腺癌细胞启动NOG，乳腺癌细胞就会侵入骨，并建立新的肿瘤转移灶。首先，NOG会增加一些成熟的破骨细胞的数量。第二，NOG保持转移性乳腺癌细胞的干细胞样的状态，这使肿瘤细胞能够传播和形成新的肿瘤转移灶。

Gomis解释：NOG表达增加乳腺癌骨转移的作用是因为它不仅影响侵略性癌症细胞固有的本能（如建立新肿瘤转移灶的能力），而且还影响骨骼环境（如导致破骨细胞变性），在这两方面共同促进乳腺癌的骨转移。

doi:10.1074/jbc.M112.355834
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Identification of NOG as a specific breast cancer bone metastasis-supporting gene.

Tarragona M, Pavlovic M, Arnal-Estape A, Urosevic J, Morales M, Guiu M, Planet E, Gonzalez-Suarez E, Gomis RR.

Metastasis requires numerous biological functions that jointly provide tumor cells from a primary site to seed and colonize a distant organ. Some of these activities are selected for in the primary site while others are acquired at the metastatic niche. We provide molecular evidence showing that the BMP inhibitor, NOG, provide metastatic breast cancer cells with the ability to colonize the bone. NOG expression is acquired during the late events of metastasis, once cells have departed from the primary site, since it is not enriched in primary tumors with high risk of bone relapse. Contrary, breast cancer bone metastatic lesions do select for high levels of NOG expression compared to metastasis to the lung, liver and brain. Pivotal to the bone colonization functions is the contribution of NOG to metastatic autonomous and non-autonomous cell functions. Using genetic approaches, we show that when NOG is expressed in human breast cancer cells facilitates bone colonization by fostering osteoclast differentiation, bone degradation and also contributes to metastatic lesions re-initiation. These findings reveal how aggressive cancer cell autonomous and non-autonomous functions can be mechanistically coupled to greater bone metastatic potential.