HAb18G/CD147 Functions in Invasion and Metastasis of Hepatocellular Carcinoma

Xu, Jing; Xu, Huiyun; Zhang, Qing; Song, Fei; Jiang, Jian‐Li; Yang, Xiang-Min; Li, Mi; Ning, Wen; Tian, Rong; Wang, Li; Yao, Hui; Feng, Qiang; Zhang, Yang; Xing, Jinliang; Zhu, Ping; Chen, Zhinan

doi:10.1158/1541-7786.mcr-06-0286

Cited by 144 publications

(140 citation statements)

References 31 publications

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“…CD147, a glycosylated immunoglobulin super family transmembrane protein, is highly expressed by HCC cells. Several in vitro studies suggest that CD147 promotes tumor invasion and metastasis, (18)(19)(20) inhibits apoptosis (21) and anoikis,promotes tumor angiogenesis, (23,24) and confers resistance to some chemotherapeutic drugs.(22) These findings indicate that CD147 might be a chemotherapeutic target for treating hepatoma. Our previous study shows that CD147 might play an important role in the inhibitory regulation of autophagy and autophagic cell death in HCC cells; (25) however, whether CD147 also plays a role in mediating the anticancer effects of berberine remains unclear.…”

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confidence: 99%

Berberine induces cell death in human hepatoma cells in vitro by downregulating CD147

Hou

Xu²,

Liu

et al. 2011

Cancer Science

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The isoquinoline plant alkaloid berberine has anti-tumor effects on a variety of carcinoma cells, mainly through inhibition of cell proliferation, apoptosis induction and cell cycle arrest. However, the mechanisms underlying its role in tumor progression are unknown. In the present study, we investigated the molecular mechanisms involved in berberine-induced cell death in human hepatoma carcinoma cell (HCC) lines HepG2 and SMMC7721. Our results showed that berberine inhibited tumor cell viability in a dose-and time-dependent manner, and induced cell death via apoptosis and autophagy. Moreover, berberine treatment significantly inhibited CD147 expression by HCC cells in a dosedependent manner. Overexpression of CD147 protein markedly reduced berberine-induced cell death. Our data provide the first experimental evidence that berberine induces cell death in HCC cells via downregulation of CD147 and suggest a new mechanism to explain its anti-tumor effects. (Cancer Sci 2011; 102: 1287-1292 B erberine is an isoquinoline alkaloid found in a number of important medicinal plant species such as Berberis aristata and Berberis aquifolium, and has antibacterial,(1) anti-hypertensive, (2) anti-inflammatory, (3) anti-diabetic (4) and anti-hyperlipidemic effects.(5) Recently, researchers have become interested in the anti-neoplastic activities of berberine and have demonstrated its anticancer effects against a variety of human cancer cells both in vitro and in vivo through suppression of tumor cell proliferation, induction of tumor cell apoptosis, and inhibition of both tumor invasion and metastasis.(6,7) These findings suggest that berberine is a promising candidate for clinical use in cancer chemotherapy.Hepatocellular carcinoma (HCC) is the sixth most common malignancy worldwide and the third leading cause of death from cancer because of its very poor prognosis. More than 1 million cases of HCC occur in the world each year.(8) Hepatocellular carcinoma is highly resistant to conventional systemic therapies and the prognosis for patients with advanced HCC remains poor. Although a lot of progress has been made in terms of chemotherapy, which provides significant survival benefits for patients with HCC, it is associated with significant side-effects, highlighting the need for therapeutic strategies that target tumor cells without compromising normal tissue function.(9,10) Thus, the development of novel systemic agents from natural products with low toxicity and few side-effects is being actively pursued. (11)(12)(13) Previous studies confirm the anti-tumor effects of berberine on HCC. (14)(15)(16) Berberine acts by inhibiting proliferation and inducing apoptosis in HCC cells. It can also inhibit the migration of HCC cells by downregulating the Rho ⁄ ROCK signaling pathway.(17) However, the exact mechanisms underlying the anti-tumor effects of berberine are still unknown. CD147, a glycosylated immunoglobulin super family transmembrane protein, is highly expressed by HCC cells. Several in vitro studies suggest that CD147 promotes...

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confidence: 99%

Berberine induces cell death in human hepatoma cells in vitro by downregulating CD147

Hou

Xu²,

Liu

et al. 2011

Cancer Science

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“…Interestingly, there is an established relationship between CD147 protein levels and hepatocarcinoma progression. Overexpression of HG-CD147 enhances the invasive ability of Hepa1-6 cells (24), and CD147 gene silence in hepatocellular carcinoma (HCC) cells significantly decreases the secretion of MMP and the invasive potential of HCC cells (25). CD147 also serves potentially as a pathological target for cancer detection of early hepatocarcinoma (26).…”

Section: Discussionmentioning

confidence: 99%

CD147 regulates vascular endothelial growth factor—A expression, tumorigenicity, and chemosensitivity to curcumin in hepatocellular carcinoma

Li¹,

Wang²,

Qu³

et al. 2007

IUBMB Life

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CD147, also named as extracelluar matrix metalloproteinase inducer (EMMPRIN), has been proved to be involved in several aspects of tumor progression. In addition to its ability to induce vascular endothelial growth factor (VEGF) production, it confers resistance to some chemotherapeutic drugs. To investigate the possible role of CD147 in the mouse hepatocarcinoma cell line Hepa1‐6 with no metastatic potential in the lymph nodes, we used RNA interference (RNAi) approach to silence CD147 expression. The results showed that silencing of CD147 in Hepa1‐6 cells significantly impeded the expression of VEGF‐A at both mRNA and protein levels. The siRNA‐treated cells exhibited significantly decreased growth ability when compared with control cells. Colony formation of CD147 deficient cells was dramatically inhibited in soft agar, and tumorigenicity was reduced in nude mice. Furthermore, the downregulation of CD147 expression also sensitized cells to be more sensitive to curcumin. These results suggested that CD147 might be a potential target for therapeutic antitumor drugs. © 2007 IUBMB IUBMB Life, 60(1): 57–63, 2008

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“…As a member of the immunoglobulin superfamily, CD147 is overexpressed in a number of epithelial cell-derived carcinomas and is associated with tumor development (20)(21)(22)(23). In previous studies, we demonstrated that the interaction of HAb18G/CD147 with integrin b1 activates the downstream FAK/PI3K-Akt signaling pathway, subsequently enhancing the malignant properties and inhibiting the chemosensitivity of HCC cells (24,25).…”

Section: Introductionmentioning

confidence: 86%

HAb18G/CD147 Promotes Radioresistance in Hepatocellular Carcinoma Cells: A Potential Role for Integrin β1 Signaling

Dang³

et al. 2015

Molecular Cancer Therapeutics

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Radiotherapy has played a limited role in the treatment of hepatocellular carcinoma (HCC) due to the risk of tumor radioresistance. A previous study in our laboratory confirmed that CD147 interacts with integrin b1 and plays an important role in modulating the malignant properties of HCC cells. In this study, we further evaluated the role of CD147 in the radioresistance of HCC and as a potential target for improving radiosensitivity. Upon irradiation, the colony formation, apoptosis, cell-cycle distribution, migration, and invasion of SMMC-7721, CD147-knockout SMMC-7721, HepG2, and CD147-knockdown HepG2 cells were determined. A nude mouse xenograft model and a metastatic model of HCC were used to detect the role of CD147 in radioresistance in vivo. Deletion of HAb18G/CD147 significantly enhanced the radiosensitivity of SMMC-7721 and HepG2 cells, and knocking out HAb18G/CD147 in SMMC-7721 cells attenuated irradiation-enhanced migration and invasion. The knockout and antibody blockade of CD147 decreased the tumor growth and metastatic potentials of HCC cells under irradiation. CD147-deleted SMMC-7721 cells showed diminished levels of calpain, cleaved talin, active integrin b1, and decreased p-FAK (Tyr397) and p-Akt (Ser473) levels. FAK and PI3K inhibitors, as well as integrin b1 antibodies, increased the radiation-induced apoptosis of SMMC-7721 cells. Our data provide evidence for CD147 as an important determinant of radioresistance via the regulation of integrin b1 signaling. Inhibition of the HAb18G/CD147 integrin interaction may improve the efficiency of radiosensitivity and provide a potential new approach for HCC therapy.

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HAb18G/CD147 Functions in Invasion and Metastasis of Hepatocellular Carcinoma

Cited by 144 publications

References 31 publications

Berberine induces cell death in human hepatoma cells in vitro by downregulating CD147

Berberine induces cell death in human hepatoma cells in vitro by downregulating CD147

CD147 regulates vascular endothelial growth factor—A expression, tumorigenicity, and chemosensitivity to curcumin in hepatocellular carcinoma

HAb18G/CD147 Promotes Radioresistance in Hepatocellular Carcinoma Cells: A Potential Role for Integrin β1 Signaling

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