Urological Cancer Center for Research and Innovation (UCCRI), St Joseph's Hospital, Hamilton, ON L8N 4A6, Canada.
Department of Surgery, McMaster University, Hamilton, ON L8S 4K1, Canada.
Genes (Basel). 2020 Mar 15;11(3):312. doi: 10.3390/genes11030312.
is a risk gene in breast and prostate cancers. Its upregulation is associated with poor prognosis of prostate cancer, breast cancer, and esophageal squamous cell carcinoma. FAM84B facilitates cancer cell proliferation and invasion in vitro, and xenograft growth in vivo. The and genes border a 1.2 Mb gene desert at 8q24.21. Co-amplification of both occurs in 20 cancer types. Mice deficient of a 430 Kb fragment within the 1.2 Mb gene desert have downregulated and expressions concurrent with reduced breast cancer growth. Intriguingly, Myc works in partnership with other oncogenes, including Ras. FAM84B shares similarities with the H-Ras-like suppressor (HRASLS) family over their typical LRAT (lecithin:retinal acyltransferase) domain. This domain contains a catalytic triad, H23, H35, and C113, which constitutes the phospholipase A and O-acyltransferase activities of HRASLS1-5. These enzymatic activities underlie their suppression of Ras. FAM84B conserves H23 and H35 but not C113 with both histidine residues residing within a highly conserved motif that FAM84B shares with HRASLS1-5. Deletion of this motif abolishes FAM84B oncogenic activities. These properties suggest a collaboration of FAM84B with Myc, consistent with the role of the gene desert in strengthening Myc functions. Here, we will discuss recent research on -derived oncogenic potential.
是乳腺癌和前列腺癌的风险基因。其上调与前列腺癌、乳腺癌和食管鳞状细胞癌的预后不良有关。FAM84B 促进体外癌细胞增殖和侵袭，以及体内异种移植物生长。和基因位于 8q24.21 处的 1.2 Mb 基因荒漠的边界。在 20 种癌症类型中都发生了这两个基因的共扩增。在 1.2 Mb 基因荒漠内缺失一个 430 Kb 片段的小鼠，其和表达下调，同时乳腺癌生长减少。有趣的是，Myc 与其他癌基因（包括 Ras）合作。FAM84B 在其典型的 LRAT（卵磷脂：视黄醇酰基转移酶）结构域上与 H-Ras 样抑制剂（HRASLS）家族具有相似性。该结构域包含一个催化三联体 H23、H35 和 C113，构成了 HRASLS1-5 的磷酸酶 A 和 O-酰基转移酶活性。这些酶活性是 HRASLS1-5 抑制 Ras 的基础。FAM84B 保留了 H23 和 H35，但不保留 C113，两个组氨酸残基都位于一个高度保守的基序内，该基序与 HRASLS1-5 共享。删除该基序会消除 FAM84B 的致癌活性。这些特性表明 FAM84B 与 Myc 合作，这与基因荒漠在增强 Myc 功能中的作用一致。在这里，我们将讨论最近关于衍生致癌潜力的研究。
