Fibulin-5 downregulates Ki-67 and inhibits proliferation and invasion of breast cancer cells

Abstract

Abstract.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.

Identification of specific biomarkers for gastric adenocarcinoma by ITRAQ proteomic approach

“…Therefore, FBLN5 acts as a tumor suppressor in ovarian cancer. Similarly, FBLN5 over expression inhibited invasion and proliferation capacity of several breast cancer lines including MCF-7, T47D and MDA-MB-23148. Interestingly, FBLN5 also prevent these cells from forming mammospheres, a key feature of cancer stem cells48.…”

“…Similarly, FBLN5 over expression inhibited invasion and proliferation capacity of several breast cancer lines including MCF-7, T47D and MDA-MB-23148. Interestingly, FBLN5 also prevent these cells from forming mammospheres, a key feature of cancer stem cells48. Thus, depending on tumor type, FBLN5 may either promote or inhibit tumor growth through mechanisms that are not totally understood.…”

Identification of the matricellular protein Fibulin-5 as a target molecule of glucokinase-mediated calcineurin/NFAT signaling in pancreatic islets

“…Fbln5 is reported to promote cell proliferation or tumor growth in mouse 3T3-L1 fibroblasts or human HT1080 fibrosarcoma cells 25 , mouse pancreatic ductal adenocarcinoma 46 , and human gastric cancer MGC-803 cells 47 . On the other hand, several previous studies have demonstrated inhibition of cell proliferation by Fbln5 overexpression in mouse vascular smooth muscle cells 18 , human breast cancer cells 48 , mink lu Mv1Lu epithelial cells 25 , primary human saphenous vein endothelial cells 49 , and rat retinal pigment epithelial cells 50 . Thus, further investigation of the pathway that mediate Fbln5 action on β-cell proliferation is required.…”

Tropomyosin isoforms have specific effects on the transcriptome of undifferentiated and differentiated B35 neuroblastoma cells

“…Interestingly, Fbln5 is reported to have context‐dependent oncogenic and tumor‐suppressing roles . Increased levels of Fbln5 reduce cell migration and invasion in ovarian and breast cancer .…”