Expression and functional analysis of FAM107 family proteins as a new molecular marker for the onco-hyperthermia therapy

我们已经确定了一个独特的分子FAM107B，一种新的热休克诱导蛋白，并将其命名为HITS。另一个FAM107家族蛋白FAM107A(TU3A/DRR1)作为候选抑癌基因已引起肿瘤学家的广泛关注。与FAM107A类似，HITS的表达缺失在多个器官的癌症中普遍存在，并参与肿瘤的生长，这与其他热休克蛋白(HSPs)如HSP70和HSP90的致癌活性形成了鲜明对比。由于HITS在不同器官中的表达下调具有组织病理学类型和临床分期特异性，HITS可作为多种肿瘤诊断的有用标记物。由于HITS和FAM107A在神经元组织中都有强表达，我们还进行了研究以阐明神经元的功能。HITS显著抑制轴突生长和细胞迁移，而FAM107A抑制作用不明显。这些结果表明，FAM107家族蛋白参与了肿瘤的发生和神经发生，具有独特的功能。

We have identified a unique molecule FAM107B, a novel heat-shock-inducible protein, and designated it HITS. The other FAM107 family protein, FAM107A (TU3A/DRR1), has attracted oncologists as a candidate tumor suppressor gene. Similar to FAM107A, loss of HITS expression is commonly observed in cancers of multiple organs and involved in tumor growth, which contrasts with oncogenic activities of other heat-shock proteins (HSPs) such as HSP70 and HSP90. Because downregulation of HITS expression was marked by histopathological-type and clinical-stage-specific manners in distinct organs, HITS can be a useful marker for diagnosis in various cancers.Since both HITS and FAM107A expressed strongly in neuronal tissues, we also investigated to elucidate neuronal functions. HITS significantly inhibits neurite outgrowth and cell migration, while FAM107A does not so much.These results suggest FAM107 family proteins are involved both in oncogenesis and neurogenesis with distinctive functions.