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Fibulin‐3 is associated with tumour progression and a poor prognosis in nasopharyngeal carcinomas and inhibits cell migration and invasion via suppressed AKT activity
Author(s) -
Hwang ChungFeng,
Chien ChihYen,
Huang ShunCheng,
Yin YuFang,
Huang ChaoCheng,
Fang FuMin,
Tsai HsinTing,
Su LiJen,
Chen ChangHan
Publication year - 2010
Publication title -
the journal of pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.964
H-Index - 184
eISSN - 1096-9896
pISSN - 0022-3417
DOI - 10.1002/path.2776
Subject(s) - nasopharyngeal carcinoma , protein kinase b , fibulin , pi3k/akt/mtor pathway , metastasis , cancer research , cancer , cell migration , medicine , biology , oncology , cell , signal transduction , gene , radiation therapy , microbiology and biotechnology , biochemistry , genetics
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. Copyright © 2010 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.