Blocking CD147 induces cell death in cancer cells through impairment of glycolytic energy metabolism

Baba, Miyako; Inoue, Masahiro; Itoh, Kazuyuki; Nishizawa, Yasuko

doi:10.1016/j.bbrc.2008.06.122

Cited by 90 publications

(70 citation statements)

References 23 publications

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“…It is a key molecule that promotes the proliferation, invasion and metastasis of cancer cells (6)(7)(8)(9)(10)(11). CD147 is an important promoter of cell growth through the reprogramming of glucose metabolism, including glycolysis (12,(24)(25)(26). These findings indicate that cancer cells use the CD147-dependent glycolytic metabolic pathways in order to divide and rapidly proliferate (12)(13)(14).…”

Section: Discussionmentioning

confidence: 99%

Overexpression of REIC/Dkk-3 suppresses the expression of CD147 and inhibits the proliferation of human bladder cancer cells

et al. 2017

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Abstract. Our group previously developed an adenoviral vector encoding the REIC/Dkk-3 gene (Ad-REIC), a tumor suppressor, for cancer gene therapy. The Ad-REIC agent induces apoptosis and inhibits invasion in a number of cancer cell lines; however, the molecular mechanisms underlying its effects remain unclear. Cluster of differentiation 147 (CD147), also known as extracellular matrix metalloproteinase inducer (EMMPRIN), is a key molecule that promotes cancer proliferation and invasion. In order to elucidate the therapeutic mechanism of Ad-REIC, its effect on the expression of CD147 in human bladder cancer KK47 cells was investigated. Treatment with Ad-REIC markedly downregulated the expression of CD147 and significantly inhibited cellular proliferation. Since the expression of CD147 is reported to be under the positive control of mitogen-activated protein kinase (MAPK) signaling and the c-Myc protein, the correlations between the expression of CD147 and the activation of MAPKs or the expression of c-Myc were examined. Unexpectedly, no positive correlation was observed between the level of CD147 and the potential regulators that were assessed, indicating that another signaling pathway is responsible for the downregulation of CD147. The results from the present study demonstrate that Ad-REIC treatment can significantly downregulate the expression of CD147 in bladder cancer cells. Downregulation of the cancer-progression factor CD147 may be a novel mechanism that underlies the therapeutic effects of Ad-REIC treatment.

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Section: Discussionmentioning

confidence: 99%

Overexpression of REIC/Dkk-3 suppresses the expression of CD147 and inhibits the proliferation of human bladder cancer cells

et al. 2017

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“…(20,35) It is well known that inhibition of CD147 suppresses tumor progression. (36)(37)(38) A previous study suggested that CD147 activates the Class I PI3K-Akt pathway in tumor cells, (39) which is one of the most important signaling pathways involved in the negative regulation of autophagy. (31) We recently confirmed that knockdown of the CD147 gene enhances autophagic cell death in HCC cells, probably by inhibiting the Class I PI3K-Akt signaling pathway.…”

Section: Discussionmentioning

confidence: 99%

“…A series of preclinical studies confirmed that inhibition of CD147 decreases tumor cell proliferation and invasion and increases chemosensitivity to therapeutic agents. (21,(36)(37)(38) However, treatments aimed at reducing CD147 expression, such as anti-CD147 monoclonal antibodies or gene silencing by RNA interference, are limited and expensive. The fact that berberine appears to downregulate CD147 directly suggests it might be a promising agent for studying the function of CD147, and for the treatment of various cancers.…”

Section: Discussionmentioning

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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“…Indeed, anti-EMMPRIN therapy has been preclinically investigated in colon cancer (27) and HNSCC (26). These studies show great potential in not only in vitro but also ex vivo models.…”

Section: Discussionmentioning

confidence: 99%

Cyclophilin A-EMMPRIN interaction induces invasion of head and neck squamous cell carcinoma

Takahashi

Suzuki

Ishikawa³

2011

Oncol Rep

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Abstract. Extracellular matrix remodeling crucial to tumorigenesis involves proteolytic enzymes, primarily matrix metalloproteinases (MMPs). MMP production is stimulated by multiple factors, including the extracellular matrix metalloproteinase inducer EMMPRIN/CD147. Overexpression of EMMPRIN, a member of the immunoglobulin superfamily, promotes invasion, metastasis, growth and survival of malignant cells. Cyclophilin A (CypA) is a multifunctional protein that promotes cancer progression in various cancer types. CypA can interact with and activate EMMPRIN; however, the role of CypA-EMMPRIN interaction in oncogenicity is not completely understood. To investigate tumorigenicity induced by the CypA-EMMPRIN interaction, we stimulated EMMPRINexpressing head and neck squamous cell carcinoma (HNSCC) cells with CypA. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide dye assay revealed that HNSCC cell proliferation increased upon stimulation of the cells with CypA, whereas cisplatin-induced cell death decreased after stimulation. Gelatin zymography showed that CypA also induced MMP-9 up-regulation. Moreover, HNSCC cell invasion through Matrigel™-coated membranes was increased upon stimulation of cells with CypA. This elevated invasive potential was abrogated by an EMMPRIN function-blocking antibody. These findings suggest that CypA, through its interaction with EMMPRIN, contributes to HNSCC tumorigenesis.

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Blocking CD147 induces cell death in cancer cells through impairment of glycolytic energy metabolism

Cited by 90 publications

References 23 publications

Overexpression of REIC/Dkk-3 suppresses the expression of CD147 and inhibits the proliferation of human bladder cancer cells

Overexpression of REIC/Dkk-3 suppresses the expression of CD147 and inhibits the proliferation of human bladder cancer cells

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

Cyclophilin A-EMMPRIN interaction induces invasion of head and neck squamous cell carcinoma

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