TSG101, a tumor susceptibility gene, bidirectionally modulates cell invasion through regulating MMP-9 mRNA expressionReportar como inadecuado




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BMC Cancer

, 15:933

Cell and molecular biology

Abstract

BackgroundTumor susceptibility gene 101 TSG101 was initially identified in fibroblasts as a tumor suppressor gene but subsequent studies show that TSG101 also functions as a tumor-enhancing gene in some epithelial tumor cells. Although previous studies have unraveled diverse biological functions of TSG101, the precise mechanism by which TSG101 is involved in carcinogenesis and tumor progression in a bidirectional and multifaceted manner remains unclear.

MethodsTo reveal the mechanism underlying bidirectional modulation of cell invasion by TSG101, we used RNA interference to examine whether TSG101 depletion bidirectionally modulated matrix metalloproteinase MMP-9 expression in different cell types.

ResultsTSG101 depletion promoted cell invasion of HT1080 cells but contrarily reduced cell invasion of HeLaS3 cells. In HT1080 cells, TSG101 depletion increased both baseline and phorbol 12-myristate 13-acetate PMA-induced MMP-9 secretion through enhancing MMP-9 mRNA expression, but did not affect the expression or activation of MMP-2. In contrast, TSG101 depletion decreased PMA-induced MMP-9 secretion through reducing MMP-9 mRNA expression in HeLaS3 cells. TSG101 depletion had little impact on the signaling pathways required for the activation of transcription of MMP-9 or MMP-9 mRNA stability in either cell line.

ConclusionTSG101 bidirectionally modulates cell invasion through regulating MMP-9 mRNA expression in different cell types. Our results provide a mechanistic context for the role of TSG101 in cell invasion as a multifaceted gene.

KeywordsTSG101 Matrix metalloproteinases Cell invasion Tumor suppressor gene Oncogene AbbreviationsTSG101Tumor susceptibility gene 101

MMPsMatrix metalloproteinases

ECMExtracellular matrix

TIMPTissue inhibitors of metalloproteinases

RNAiRNA interference

FCSFetal calf serum

GAPDHGlyceraldehyde-3-phosphate dehydrogenase

siRNASmall interfering RNA

PBSPhosphate buffered saline

PMAPhorbol 12-myristate 13-acetate

BSABovine serum albumin

RTReverse transcription

Xu Bin Sai and Tomohiko Makiyama contributed equally to this work.

Electronic supplementary materialThe online version of this article doi:10.1186-s12885-015-1942-1 contains supplementary material, which is available to authorized users.

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Autor: Xu Bin Sai - Tomohiko Makiyama - Hiroshi Sakane - Yukimi Horii - Hideyuki Hiraishi - Hiromichi Shirataki

Fuente: https://link.springer.com/







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