Fibulin‐3 is associated with tumour progression and a poor prognosis in nasopharyngeal carcinomas and inhibits cell migration and invasion via suppressed AKT activity

Abstract

Nasopharyngeal carcinoma (NPC) is known for its highly metastatic character. Recent advances in diagnosis and treatment have not improved the high mortality rate that is attributable to early metastasis. Although several biomarkers correlate with metastasis and prognosis, the molecular mechanisms of NPC development and progression remain unclear. We demonstrate comprehensively that fibulin-3 is down-regulated in NPC. Loss of fibulin-3 expression is significantly correlated with advanced tumour and lymph node-metastasis stages, and indicates a poor 5-year survival rate. Functionally, fibulin-3 has the ability to suppress cell migration and invasion in NPC cancer cells by decreasing the activity of phospho-AKT. Conversely, its depletion by fibulin-3-mediated siRNAs may elevate phospho-AKT activity and significantly enhance the ability of NPC cancer cells to migrate and invade. Consistent with this negative association between fibulin-3 and phospho-AKT, their expression levels are inversely correlated in NPC specimens by immunohistochemical analysis. Thus, lower fibulin-3 expression is an important indicator of poor survival. It may also contribute to the development of new therapeutic strategies to block the PI3K/AKT pathway in NPC cancer cells.

Fibulin-3 promoter methylation alters the invasive behavior of non-small cell lung cancer cell lines via MMP-7 and MMP-2 regulation

“…Conversely, fibulin-is down-regulated in primary breast tumours, lung cancer and fibrosarcomas (6,14,34) and is thought to inhibit tumour growth. Fibulin-3 is also down-regulated in nasopharyngeal carcinomas and involved in regulation of invasiveness (35). These results suggest that fibulin-3 has dual functions as a positive and negative regulator of cancer cell growth depending on cell type, although its function as a cell modulator is not clearly understood.…”

Prognostic value of several biomarkers for the patients with malignant pleural mesothelioma

“…Although originally characterized as components of elastic fibers in connective tissue, fibulin-3 has been implicated in cell morphology, growth, adhesion, and motility, especially in tumorigenesis [43]. However, current studies conclude that both tumor suppressive functions and oncogenic activities of fibulin-3 can be exhibited in human cancers [44][45][46][47][48]. In 2012, Pass and his colleagues [49] for the first time claimed that fibulin-3 was a highly promising biomarker, which could perform well in the diagnosis and prognosis for MPM.…”

Assessing the association between EFEMP1 rs3791679 polymorphism and risk of glioma in a Chinese Han population

“…Previous studies have reported that the EFEMP1 gene plays a role in several types of cancers, such as lung cancer, liver cancer, breast cancer, prostate cancer, and nasopharyngeal cancer (Yue et al, 2007;Sadr-Nabavi et al, 2009;Hwang et al, 2010;Nomoto et al, 2010;Kim et al, 2011;Zhang et al, 2011). Yue et al (2007) reported that alterations in the expression of EFEMP1 could inhibit lung cancer-cell growth, resulting in a high tumor grade.…”

“…Sadr-Nabavi et al (2009) investigated the role of EFEMP1 in human breast cancer, and reported an association between reduced EFEMP1 expression and the development of sporadic breast cancer and epigenetic alterations. Hwang et al (2010) reported that fibulin-3 could suppress cell migration and invasion in nasopharyngeal cancer cells in a Taiwanese population. Furthermore, Nomoto et al (2010) reported that EFEMP1 was significantly down-regulated in tumor tissues, and that promoter methylation of the EFEMP1 gene could be a marker for the prognosis of hepatocellular carcinoma.…”