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“Background Hepatocellular carcinoma (HCC), also called hepatoma, is the most frequent type of primary liver cancer and one of the leading causes of cancer death worldwide, which caused over 600,000 deaths per year [1]. Invasion and metastasis are the most critical reason for the poor prognosis of HCC patients [2]. Glucose-regulated protein 78(GRP78)

is present at a basal level in normal tissues. However it is overexpressed in almost all the human cancers SB203580 and plays important role in anti-apoptotic process of cancer cells [3]. GRP78, which has been regarded as a endoplasmic reticulum(ER) chaperone previously, is a multifunctional protein [4, 5]. Recently, lots of data have demonstrated that Grp78 is involved in the regulation of invasion and metastasis of many human cancers including breast, prostate, gastric, lung, liver cancers [6–10]. Although we have reported that GRP78 facilitates the invasion of hepatocellular carcinoma cells, whether GRP78 plays a role in ECM degradation is still not determined. The invasion and metastasis of cancer cells is a complex process which is mainly determined by the following events: about (1) extracellular matrix (ECM) degradation, (2) the arrangement of cytoskeleton, (3) cell polarity formation [11–13]. These processes are tightly regulated by temporally and spatially regulated expression and activation of many signal molecules including focal adhesion kinase (FAK),

Src, c-Jun N-terminal kinase (JNK) [14, 15]. Matrix metalloproteinases (MMPs) are a family of related zinc-dependent proteinases that degrade most extracellular matrix [16]. So far, nearly 20 members of the MMP family that share common structural and functional elements have been identified [17]. Among them, MMP-2 and MMP-9 are the most concerned and their functions have been well-characterized. They are believed to play important role in the invasive process and high level expression or activation of MMPs is associated with the invasion and metastasis of cancer cells [18]. The activity of MMP-2 and MMP-9 is regulated by many factors. Recent studies have revealed that the membrane type metalloproteinases (MT-MMP) and the tissue inhibitor of metalloproteinases (TIMP) play coordinately in the regulation of MMPs activity.