DNA aptamers against exon v10 of CD44 inhibit breast cancer cell migration.
DNA aptamers against exon v10 of CD44 inhibit breast cancer cell migration.
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DOI：
10.1371/journal.pone.0088712
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Shriver CD
中科院分区：
文献类型：
--
作者：
Iida J;Clancy R;Dorchak J;Somiari RI;Somiari S;Cutler ML;Mural RJ;Shriver CD
CD44黏附分子在许多乳腺癌细胞中表达，并已被证明在调节恶性表型如生长、迁移和侵袭方面发挥关键作用。CD44是一种由单个20外显子基因编码的完整跨膜蛋白。CD44生物学功能的多样性是这些外显子不同剪接变体的结果。已有研究表明CD44外显子V10在促进肿瘤侵袭转移中起关键作用，但其分子机制尚不清楚。鉴于外显子V10位于CD44的胞外区，我们推测CD44通过外显子V10与其他细胞表面分子形成分子复合体，以促进乳腺癌细胞的迁移。为了验证这一假设，我们选择了与CD44外显子V10特异结合的DNA适配子，使用指数浓缩配体系统进化(SELEX)。我们选择了抑制乳腺癌细胞迁移的适体。免疫共沉淀研究表明，EphA2与CD44共沉淀。下拉研究表明，重组CD44外显子V10与EphA2结合，更重要的是，抑制迁移的适体也阻止了EphA2与外显子V10的结合。这些结果表明，CD44与EphA2在乳腺癌细胞表面形成了分子复合体，该复合体在促进乳腺癌转移中起着关键作用。这些结果不仅为表征乳腺癌转移的机制提供了洞察力，也为开发针对乳腺癌和可能表达CD44外显子V10的其他癌症类型的靶向特异性治疗提供了洞察力。
CD44 adhesion molecules are expressed in many breast cancer cells and have been demonstrated to play a key role in regulating malignant phenotypes such as growth, migration, and invasion. CD44 is an integral transmembrane protein encoded by a single 20-exon gene. The diversity of the biological functions of CD44 is the result of the various splicing variants of these exons. Previous studies suggest that exon v10 of CD44 plays a key role in promoting cancer invasion and metastasis, however, the molecular mechanisms are not clear. Given the fact that exon v10 is in the ectodomain of CD44, we hypothesized that CD44 forms a molecular complex with other cell surface molecules through exon v10 in order to promote migration of breast cancer cells. In order to test this hypothesis, we selected DNA aptamers that specifically bound to CD44 exon v10 using Systematic Evolution of Ligands by Exponential Enrichment (SELEX). We selected aptamers that inhibited migration of breast cancer cells. Co-immunoprecipitation studies demonstrated that EphA2 was co-precipitated with CD44. Pull-down studies demonstrated that recombinant CD44 exon v10 bound to EphA2 and more importantly aptamers that inhibited migration also prevented the binding of EphA2 to exon v10. These results suggest that CD44 forms a molecular complex with EphA2 on the breast cancer cell surface and this complex plays a key role in enhancing breast cancer migration. These results provide insight not only for characterizing mechanisms of breast cancer migration but also for developing target-specific therapy for breast cancers and possibly other cancer types expressing CD44 exon v10.
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影响因子：
5.6
作者：
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通讯作者：
BOURGUIGNON, LYW
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3.7
作者：
Iida J;Dorchak J;Lehman JR;Clancy R;Luo C;Chen Y;Somiari S;Ellsworth RE;Hu H;Mural RJ;Shriver CD
通讯作者：
Shriver CD