Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Oviedo, Oviedo, Spain.
Department of Morphology and Cellular Biology, Faculty of Medicine, University of Oviedo, Oviedo, Spain.
Int J Oncol. 2016 Apr;48(4):1447-56. doi: 10.3892/ijo.2016.3394. Epub 2016 Feb 17.
Fibulins not only function as molecular bridges within the cellular microenvironment but also influence cell behavior. Thus, fibulins may contribute to create a permissive microenvironment for tumor growth but can also stimulate different mechanisms that may impede tumor progression. This is the case with Fibulin-5, which has been shown to display both tumor-promoting and tumor-protective functions by mechanisms that are not totally defined. We show new evidence on the tumor-protective functions displayed by Fibulin-5 in MCF-7, T47D and MDA-MB-231 breast cancer cells including the inhibition of invasion and proliferation capacity and hampering the ability to form mammospheres. Reduction in the level of phosphorylation of Ser residues involved in the nuclear translocation of β-catenin may underlie these antitumor effects. We also found that Fibulin-5 reduces the level of expression of Ki-67, a nuclear protein associated with cell proliferation. Moreover, reduction in Fibulin-5 expression corresponds to an increase of Ki-67 detection in breast tissue samples. Overall, our data provide new insights into the influence of Fibulin-5 to modify breast cancer cell behavior and contribute to better understand the connections between fibulins and cancer.
纤连蛋白不仅在细胞微环境中充当分子桥，还影响细胞行为。因此，纤连蛋白可能有助于为肿瘤生长创造一个允许的微环境，但也可能刺激不同的机制，从而阻碍肿瘤的进展。纤连蛋白-5 就是这种情况，其通过尚未完全确定的机制显示出既促进肿瘤又保护肿瘤的功能。我们在 MCF-7、T47D 和 MDA-MB-231 乳腺癌细胞中展示了纤连蛋白-5 显示出的肿瘤保护功能的新证据，包括抑制侵袭和增殖能力，并阻碍形成乳腺球体的能力。参与 β-连环蛋白核易位的 Ser 残基磷酸化水平的降低可能是这些抗肿瘤作用的基础。我们还发现纤连蛋白-5 降低了与细胞增殖相关的核蛋白 Ki-67 的表达水平。此外，纤连蛋白-5 表达的减少对应于在乳腺组织样本中 Ki-67 检测的增加。总的来说，我们的数据提供了对纤连蛋白-5 改变乳腺癌细胞行为的影响的新见解，并有助于更好地理解纤连蛋白与癌症之间的联系。
