N-cadherin promotes motility in human breast cancer cells regardless of their E-cadherin expression.

N-cadherin promotes motility in human breast cancer cells regardless of their E-cadherin expression.
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DOI:
10.1083/jcb.147.3.631
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发表时间:
1999-11-01
影响因子:
7.8
通讯作者:
Wheelock, M J
Wheelock, M J
中科院分区:
生物学1区
文献类型:
--
作者:
Nieman, M T;Prudoff, R S;Johnson, K R;Wheelock, M J

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E-钙粘蛋白是一种跨膜糖蛋白,介导钙依赖性同型细胞间粘附,并在维持上皮细胞的正常表型中发挥作用。 E-钙粘蛋白表达的降低与乳腺癌侵袭性的增加相关。在其他系统中,上皮细胞对非上皮钙粘蛋白(例如 N-钙粘蛋白)的不当表达已被证明会下调 E-钙粘蛋白的表达并导致分散的表型。在这项研究中,我们探讨了非上皮钙粘蛋白的表达可能与乳腺癌细胞的运动性和侵袭性增加相关的可能性。我们发现 N-钙粘蛋白促进运动和侵袭; E-钙粘蛋白表达的降低并不一定与运动或侵袭相关; N-钙粘蛋白表达与侵袭和运动相关,并且可能在促进运动中发挥直接作用;在侵袭性 N-钙粘蛋白阳性细胞中强制表达 E-钙粘蛋白不会降低其运动性或侵袭能力;在非侵袭性 E-钙粘蛋白阳性细胞中强制表达 N-钙粘蛋白会产生侵袭性细胞,即使这些细胞继续表达高水平的 E-钙粘蛋白; N-钙粘蛋白依赖性运动可能是由 FGF 受体信号传导介导的; cadherin-11 以类似于 N-cadherin 的方式促进上皮细胞运动。
E-cadherin is a transmembrane glycoprotein that mediates calcium-dependent, homotypic cell–cell adhesion and plays a role in maintaining the normal phenotype of epithelial cells. Decreased expression of E-cadherin has been correlated with increased invasiveness of breast cancer. In other systems, inappropriate expression of a nonepithelial cadherin, such as N-cadherin, by an epithelial cell has been shown to downregulate E-cadherin expression and to contribute to a scattered phenotype. In this study, we explored the possibility that expression of nonepithelial cadherins may be correlated with increased motility and invasion in breast cancer cells. We show that N-cadherin promotes motility and invasion; that decreased expression of E-cadherin does not necessarily correlate with motility or invasion; that N-cadherin expression correlates both with invasion and motility, and likely plays a direct role in promoting motility; that forced expression of E-cadherin in invasive, N-cadherin–positive cells does not reduce their motility or invasive capacity; that forced expression of N-cadherin in noninvasive, E-cadherin–positive cells produces an invasive cell, even though these cells continue to express high levels of E-cadherin; that N-cadherin–dependent motility may be mediated by FGF receptor signaling; and that cadherin-11 promotes epithelial cell motility in a manner similar to N-cadherin.