Keratin 19 maintains E-cadherin localization at the cell surface and stabilizes cell-cell adhesion of MCF7 cells.

Keratin 19 maintains E-cadherin localization at the cell surface and stabilizes cell-cell adhesion of MCF7 cells.
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DOI:
10.1080/19336918.2020.1868694
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发表时间:
2021-12
影响因子:
3.2
通讯作者:
Chung BM
Chung BM
中科院分区:
生物学3区
文献类型:
--
作者:
Alsharif S;Sharma P;Bursch K;Milliken R;Lam V;Fallatah A;Phan T;Collins M;Dohlman P;Tiufekchiev S;Nehmetallah G;Raub CB;Chung BM

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细胞骨架蛋白角蛋白 19 (K19) 在乳腺癌中高表达,但其对乳腺癌细胞力学的影响尚不清楚。在 K19 表达被消除的 MCF7 细胞中,我们发现 K19 是维持圆形上皮样形状和紧密细胞间粘附所必需的。 K19 的缺失也会降低细胞表面 E-钙粘蛋白水平。抑制内化可恢复 KRT19 敲除细胞的细胞间粘附,表明 E-钙粘蛋白内化导致粘附缺陷。最终,虽然 K19 抑制细胞迁移和侵袭,但它是细胞在悬浮液中形成集落所必需的。我们的结果表明,K19 可以稳定细胞膜上的 E-钙粘蛋白复合物,以维持细胞间粘附,从而抑制细胞侵袭性,但为循环肿瘤细胞提供生长和存活优势。
A cytoskeletal protein keratin 19 (K19) is highly expressed in breast cancer but its effects on breast cancer cell mechanics are unclear. In MCF7 cells where K19 expression is ablated,we found that K19 is required to maintain rounded epithelial-like shape and tight cell-cell adhesion. A loss of K19 also lowered cell surface E-cadherin levels. Inhibiting internalization restored cell-cell adhesion of KRT19 knockout cells, suggesting that E-cadherin internalization contributed to defective adhesion. Ultimately, while K19 inhibited cell migration and invasion, it was required for cells to form colonies in suspension. Our results suggest that K19 stabilizes E-cadherin complexes at the cell membrane to maintain cell-cell adhesion which inhibits cell invasiveness but provides growth and survival advantages for circulating tumor cells.
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