Abstract
Integrin subunit alpha 9 (ITGA9) mediates cell-cell and cell-matrix adhesion, cell migration, and invasion through binding different kinds of extracellular matrix (ECM) components. However, its potential role and underlying molecular mechanisms remain unclear in hepatocellular carcinoma (HCC). Here, we found that ITGA9 expression was obviously decreased in patients with HCC, which was negatively correlated with HCC growth and metastasis. ITGA9 overexpression significantly inhibited cell proliferation and migration in vitro as well as tumor growth and metastasis in vivo. Our data demonstrated that the inhibitory effect of ITGA9 on HCC cell motility was associated with reduced phosphorylation of focal adhesion kinase (FAK) and c-Src tyrosine kinase (Src), disrupted focal adhesion reorganization, and decreased Rac1 and RhoA activity. Our data suggest ITGA9, as a suppressor of HCC, prevents tumor cell migration and invasiveness through FAK/Src-Rac1/RhoA signaling.
Highlights
Hepatocellular carcinoma (HCC) is a highly malignant solid tumor which results in chronic inflammation in the liver [1]
We found that Integrin subunit alpha 9 (ITGA9) mRNA level was downregulated in HCC compared to corresponding noncancerous liver (CNL) tissues (Figure 1(a))
Given that no dominant mechanism is responsible for HCC cell growth and metastasis, efforts aiming at identifying novel molecules may exert therapeutic benefits for patients suffering from HCC
Summary
Hepatocellular carcinoma (HCC) is a highly malignant solid tumor which results in chronic inflammation in the liver [1]. The principal character of HCC is early metastasis and poor prognosis. A series of changes in the tumor microenvironment (TME) are involved in the progression of HCC [3]. The adaptation of cancer cells to its surrounding microenvironment depends on the interaction between the extracellular matrix (ECM) with membrane receptors [4]. Many molecules in TME have been reported to influence tumor development by regulating tumor cell proliferation, apoptosis, and motility [5,6,7]. It has been shown that integrin receptors and its downstream signal molecules, including Src, FAK, and p130Cas, have a remarkable influence on tumor progression and metastasis [8]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
