CD151 Amplifies Signaling by Integrin α6β1 to PI3K and Induces the Epithelial–Mesenchymal Transition in HCC Cells

Ke, Ai–Wu; Shi, Guo‐Ming; Zhou, Jian; Huang, Xiaoyong; Shi, Ying‐Hong; Ding, Zhen–Bin; Wang, Xiao–Ying; Devbhandari, Ranjan Prasad; Fan, Jia

doi:10.1053/j.gastro.2011.02.008

Cited by 146 publications

(176 citation statements)

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“…5,[9][10][11][12][13][14] Epithelialmesenchymal transition (EMT) has a critical role in the early stages of dissemination of malignant epithelial tumors leading to metastatic spread. 15 There is growing evidence that LAMC2 expression increases in the carcinoma cells undergoing EMT, [16][17][18] and that level of LAMC2 expression is regulated directly by the EMT master regulator ZEB1 and activated β-catenin in invasive colorectal carcinoma cells. 19,20 Combining results of gene expression microarrays with a metastasis selection model in mice, we found a robust association between metastatic derivatives of A549 lung ADC cells and increased expression of LAMC2.…”

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confidence: 99%

LAMC2 enhances the metastatic potential of lung adenocarcinoma

et al. 2015

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Lung cancer is the number one cancer killer, and metastasis is the main cause of high mortality in lung cancer patients. However, mechanisms underlying the development of lung cancer metastasis remain unknown. Using genome-wide transcriptional analysis in an experimental metastasis model, we identified laminin γ2 (LAMC2), an epithelial basement membrane protein, to be significantly upregulated in lung adenocarcinoma metastatic cells. Elevated LAMC2 increased traction force, migration, and invasion of lung adenocarcinoma cells accompanied by the induction of epithelial-mesenchymal transition (EMT). LAMC2 knockdown decreased traction force, migration, and invasion accompanied by EMT reduction in vitro, and attenuated metastasis in mice. LAMC2 promoted migration and invasion via EMT that was integrin β1-and ZEB1-dependent. High LAMC2 was significantly correlated with the mesenchymal marker vimentin expression in lung adenocarcinomas, and with higher risk of recurrence or death in patients with lung adenocarcinoma. We suggest that LAMC2 promotes metastasis in lung adenocarcinoma via EMT and may be a potential therapeutic target. Cell Death and Differentiation (2015) 22, 1341-1352; doi:10.1038/cdd.2014.228; published online 16 January 2015Lung cancer is the leading cause of cancer-related death. 1 Non-small-cell lung cancer (NSCLC) accounts for~80-85% of lung cancers. 2 Only 20-30% of NSCLC are radically resectable and the majority of lung cancer patients succumb to the disease. The high mortality of NSCLC is largely attributable to late diagnosis, when metastases are present. 2 The molecular mechanisms governing metastasis of NSCLC remain poorly understood.Metastasis is a complex, multistep process, involving migration and invasion of malignant cells from the primary tumor to blood vessels, intravasation, and survival in the circulation, and ultimately extravasation, colonization, and formation of secondary tumor at distant target organs. 3 Each of these events is classically driven by the acquisition of genetic and/or epigenetic traits in tumor cells and the cooperation of nonneoplastic stromal cells. Increased or decreased expression of several genes in tumors has been found to be correlated with metastasis. 3 However, specific gene alterations that drive NSCLC metastasis remain largely elusive.Laminin γ2 (LAMC2) is a subunit of the heterotrimeric glycoprotein laminin-332 (LAM-332, formerly laminin-5), consisting of the α3, β3, and γ2 chains. Although LAMC2 is an important structural component of the epithelial basement membrane (BM) in various normal tissues, 4 there is an emerging evidence for a pathological role of LAMC2 monomer in cancer. It has been demonstrated that LAMC2 protein expression correlates with clinical outcome of stage I lung adenocarcinoma (ADC) patients. 5,6 In addition, noncontinuous expression pattern of LAMC2 predicts the prognosis of esophageal squamous cell carcinoma (SCC), 7 and secreted LAMC2 in the serum is associated with the aggressiveness of pancreatic cancer. 8 Besides, LAMC2 monom...

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confidence: 99%

LAMC2 enhances the metastatic potential of lung adenocarcinoma

et al. 2015

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“…Proteins extracted from RPMVECs were analyzed by immunoblotting as described elsewhere [14]. Briefly, near confluent cells were collected as low-speed pellets and homogenized in TM-PI buffer supplemented with EDTA (0.5 mM) and NaF (10 mM).…”

Section: Western Blot Analysismentioning

confidence: 99%

“…Fifty micrograms of total protein from the supernatant obtained after centrifugation at 100,000 × g was precipitated using methanolchloroform, re-dissolved in loading buffer, and subjected to 10% polyacrylamide gel electrophoresis followed by electrotransfer to a nitrocellulose membrane (Schleicher & Schuell, Inc.). After 1 h pre-incubation with 1% blocking buffer (Boehringer Mannheim) at room temperature, immunoblotting was performed with different antibodies as described elsewhere [14]. Membranes were incubated in POD conjugated secondary IgG antibodies and the immunoreactivity was visualized using the BM Teton POD substrate (Boehringer Mannheim) and 1.5% hydrogen peroxide.…”

Section: Western Blot Analysismentioning

confidence: 99%

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Simvastatin attenuates the lipopolysaccharideinduced inflammatory response of rat pulmonary microvascular endothelial cells by downregulating toll-like receptor 4 expression

Ding

et al. 2014

Open Medicine

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“…[20][21][22] CD151 has also been implicated in epithelialmesenchymal transition (EMT) of hepatocellular carcinoma (HCC) promoting a motile phenotype of these cells. 23 CD151, together with integrin a3b1, located at the periphery of specialized surface protrusions-invadopodia, was found to regulate expression and activity of MMPs. 7,24 Finally, numerous studies using in vitro and in vivo models of cancer implicate CD151 in the promotion of metastasis.…”

Section: Introductionmentioning

confidence: 98%

CD151 in cancer progression and metastasis: a complex scenario

Sądej

Grudowska

Turczyk

et al. 2014

Laboratory Investigation

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Originally identified as a molecular organizer of interacting proteins into tetraspanin-enriched microdomains, the tetraspanin CD151 has now been shown to be involved in tumour progression. Increasing evidence emerging from in vitro, in vivo and clinical analyses implicates this tetraspanin in supporting growth of various types of tumours at different levels. It affects both cell autonomous behavior and communication with neighboring cells and the microenvironment. CD151 regulates post-adhesion events, that is, cell spreading, migration and invasion including subsequent intravasation and formation of metastasis. Present on both neoplastic and endothelial cells, CD151 is engaged in promotion of tumour neovascularization. The molecular mechanism of CD151 in cancer is based on its ability to organize distribution and function of interacting proteins, ie, laminin-binding integrins (a3b1, a6b1 and a6b4), receptors for growth factors (HGFR, EGFR and TGF-b1R) and matrix metalloproteinases (MMP-7, MMP-2 and MMP-9), which indicates its importance in disease development. Results of clinical analyses of CD151 expression in different types of cancer and a large number of in vivo models demonstrate its impact on tumour growth and invasion and implicate CD151 as a valuable diagnostic and prognostic marker as well as a potential target for anti-cancer therapy. INTRODUCTIONTumour cells progress through multiple orchestrated steps before metastatic lesions are established in distant organs. These steps include detachment from the primary tumour mass, invasion of the basement membrane, migration through the surrounding extracellular matrix (ECM) followed by intravasation and extravasation and, finally, colonization of a secondary anatomical site. Successful completion of this sequence requires intrinsic changes enabling phenotypic transformation of the cell and, at every step, its coordinated communication with the tumour's microenvironment. A complex network of intricate tumourstroma interactions involves integrin-dependent adhesion and cell migration on the ECM, ECM degradation by matrix metalloproteinases (MMPs), and activation of signalling pathways responsible for cell survival, proliferation and motility, triggered by growth factor receptors stimulated by the environment.

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CD151 Amplifies Signaling by Integrin α6β1 to PI3K and Induces the Epithelial–Mesenchymal Transition in HCC Cells

Cited by 146 publications

References 48 publications

LAMC2 enhances the metastatic potential of lung adenocarcinoma

LAMC2 enhances the metastatic potential of lung adenocarcinoma

Simvastatin attenuates the lipopolysaccharideinduced inflammatory response of rat pulmonary microvascular endothelial cells by downregulating toll-like receptor 4 expression

CD151 in cancer progression and metastasis: a complex scenario

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