Stimulatory role of nectin‐4 and p95‐ErbB2 in multilayered T47D cell proliferation
Stimulatory role of nectin‐4 and p95‐ErbB2 in multilayered T47D cell proliferation
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DOI：
10.1111/gtc.12940
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发表时间：
2022-04
期刊：
影响因子：
2.1
通讯作者：
Shin Kedashiro;T. Kameyama;Kiyohito Mizutani;Y. Takai
中科院分区：
文献类型：
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作者：
Shin Kedashiro;T. Kameyama;Kiyohito Mizutani;Y. Takai
在贴壁培养和悬浮培养中增殖是癌细胞的特征。我们之前使用T47D人乳腺癌细胞发现，在许多癌细胞中上调的连接素- 4与ErbB2及其抗曲妥珠单抗剪接变体p95 - ErbB2和ErbB2ΔEx16顺式相互作用，并在贴壁培养中主要通过PI3K - AKT途径增强DNA合成。我们在这里发现，只有nectin‐4和p95‐ErbB2的结合，而不是nectin‐4和ErbB2或nectin‐4和ErbB2ΔEx16的结合，通过Hippo通路介导的SOX2基因表达，在贴贴培养中协同增强了多层T47D细胞的增殖。T47D细胞表达由粘附连接（AJs）、紧密连接和细胞极性分子组成的apical junctional complex （AJC）组分，但不表达afadin。T47D细胞的AJC和顶基极性在单层中紊乱，而T47D细胞在多层中稳定表达连接素- 4和p95 - ErbB2。这些结果表明，在贴壁培养中，连接素- 4和p95 - ErbB2在多层增殖中起刺激作用。
Multilayered proliferation in an adherent culture as well as proliferation in a suspension culture is a characteristic feature of cancer cells. We previously showed using T47D human mammary cancer cells that nectin‐4, upregulated in many cancer cells, cis‐interacts with ErbB2 and its trastuzumab‐resistant splice variants, p95‐ErbB2 and ErbB2ΔEx16, and enhances DNA synthesis mainly through the PI3K‐AKT pathway in an adherent culture. We showed here that only the combination of nectin‐4 and p95‐ErbB2, but not that of nectin‐4 and ErbB2 or that of nectin‐4 and ErbB2ΔEx16, cooperatively enhanced multilayered T47D cell proliferation through the Hippo pathway–mediated SOX2 gene expression in an adherent culture. T47D cells expressed the components of the apical junctional complex (AJC) consisting of adherens junctions (AJs) and tight junctions and cell polarity molecules, but not the AJ component afadin. The AJC and apicobasal polarity were disorganized in T47D cells in a monolayer and T47D cells stably expressing both nectin‐4 and p95‐ErbB2 in multilayers. These results indicate that nectin‐4 and p95‐ErbB2 play a stimulatory role in multilayered proliferation in an adherent culture.