The Role of CD44 in Glucose Metabolism in Prostatic Small Cell Neuroendocrine Carcinoma

Li, Wei; Cohen, Arthur M.; Sun, Yin; Squires, Jill; Braas, Daniel; Graeber, Thomas G.; Du, Lin; Li, Gang; Li, Zhen; Xu, Xin; Chen, Xufeng; Huang, Jiaoti

doi:10.1158/1541-7786.mcr-15-0466

Cited by 40 publications

(56 citation statements)

References 32 publications

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“…Ablation of CD44 induces glycolysis-to-oxidative phosphorylation transition (21). Inhibition of CD44 also sensitized prostate cancer cells to carboplatin (22). Reduction of STAT3 and CD44 expression has a significant impact on the study of corilagin mechanisms.…”

Section: Discussionmentioning

confidence: 99%

“…Snail and other transcription factors, such as STAT3 and CD44, are known to regulate glycolysis (16)(17)(18)(19)(20)(21)(22)(23), and then further affect tumor growth. To validate the iTRAq proteomics results, we investigated whether corilagin affects glycolysis.…”

Section: Corilagin Inhibits the Glycolysis Pathways Via Snailmentioning

confidence: 99%

“…6), both of which have been demonstrated to be crucial for glycolysis regulation (18)(19)(20)(21)(22)(23). Corilagin showed strong inhibition of Snail in HOPM-Snail cells, compared with HOPM cells.…”

Section: Corilagin Inhibits the Glycolysis Pathways Via Snailmentioning

confidence: 99%

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Corilagin sensitizes epithelial ovarian cancer to chemotherapy by inhibiting Snail-glycolysis pathways

et al. 2017

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Abstract. We identified that corilagin is a major component extracted from a well-known hepatoprotective and antiviral medicinal herb, Phyllanthus niruri L with antitumor activity. Our previous study found that corilagin inhibited the growth of ovarian cancer cells via the TGF-β/AKT/ERK signaling pathways. Recently, we demonstrated that corilagin enhanced the sensitivity of ovarian cancer cells to chemotherapy. Ovarian cancer cell lines, SKOv3ip, Hey and HO-8910PM-Snail, were treated with different concentrations of corilagin in combination with paclitaxel and carboplatin. Corilagin distinctly enhanced the inhibitory effects of paclitaxel and carboplatin. To understand the mechanisms involved in the chemo-sensitization by corilagin, we performed reverse phase protein array analysis to determine the signaling networks induced by corilagin. We observed that both paclitaxel and carboplatin upregulated the expression levels of several apoptotic and death-related proteins, such as caspase 3, caspase 7 and PDCD4, which were further enhanced when combined with corilagin. Meanwhile, corilagin induced distinct pathways to paclitaxel and carboplatin treatment. We also performed isobaric tags for relative and absolute quantitation proteomics analysis in corilagen-treated ovarian cancer cells. This analysis indicated that corilagin is mainly involved in the glycolysis pathway. Seahorse XF96 extracellular acidification rate analysis confirmed that corilagin inhibited glycolysis by downregulation of CD44 and STAT3. In summary, our observations indicate that corilagin sensitized epithelial ovarian cancer cells to paclitaxel and carboplatin treatment by primarily inhibiting Snail-glycolysis pathways. Corilagin is a herbal medicine with low toxic effects to normal cells, particularly hepatoprotective, and may be an ideal complimentary medicine when combined with highly toxic chemotherapeutic agents. IntroductionCorilagin (C 27 H 22 O 18 ), a gallotannin found in many plants, is a major active component of many ethnopharmacological plants, such as Phyllanthus niruri L., P. emblica L. and P. urinaria L. Corilagin was first isolated in 1951 by Schmidt and Lademann from Divi-divi (Caesalpina coriaria) plants (1). In the past few decades, corilagin has been reported to display several pharmacological activities, including antioxidant (2), hepatoprotective (3), anti-inflammatory (4), neural system protective (5) and cardiovascular protective (6) activities, and has been found to be beneficial in managing type 2 diabetes (7). Recently, its antitumor effects in hepatocellular carcinoma (8,9), ovarian cancer (10) and cholangiocarcinoma (11) have attracted attention.Since 2005, we screened hundreds of herbs, among which Phyllanthus niruri L. has the highest anticancer potential. The present study further identified that corilagin is a major active component from P. niruri L. extracts and has broadspectrum antitumor activity, a better antitumor potential but lower toxicity to normal cells (12). It is effective in retarding the growth of he...

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Section: Discussionmentioning

confidence: 99%

Section: Corilagin Inhibits the Glycolysis Pathways Via Snailmentioning

confidence: 99%

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Corilagin sensitizes epithelial ovarian cancer to chemotherapy by inhibiting Snail-glycolysis pathways

et al. 2017

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“…CD44 is found to regulate expression of the PFKFB4 enzyme in prostatic PC-3 cells (SCNC) as knockdown of CD44 reduced expression of protein and mRNA of PFKFB4 and also increased ROS levels [31,32]. Knockdown of CD44 also increased the sensitivity of SCNC tumor cells to carboplatin [32]. These reports confirm the multifaceted role of CD44 in the progression of cancer.…”

Section: Regulation Of Cancer Cell Metabolism By Cd44mentioning

confidence: 58%

“…In small cell neuroendocrine carcinoma (SCNC) of the prostate, it is found to be highly expressed as compared to adenocarcinoma cells of the prostate. CD44 is found to regulate expression of the PFKFB4 enzyme in prostatic PC-3 cells (SCNC) as knockdown of CD44 reduced expression of protein and mRNA of PFKFB4 and also increased ROS levels [31,32]. Knockdown of CD44 also increased the sensitivity of SCNC tumor cells to carboplatin [32].…”

Section: Regulation Of Cancer Cell Metabolism By Cd44mentioning

confidence: 99%

CD44: A Multifaceted Molecule in Cancer Progression

Sharma¹

2017

JCPCR

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CD44, a single pass transmembrane glycoprotein, initially characterized as lymphocyte homing receptor, has now been implicated in various stages of cancer development. The Anomaly in CD44 expression distinguishes most human cancers. CD44 is also identified as cancer stem cell marker. This review will comprehend the versatile role of CD44 during cancer initiation, proliferation, invasion, metastasis and as the regulator of cancer cell metabolism.

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The CD147‐HYALURONAN Axis in Cancer

Toole

2019

The Anatomical Record

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CD147 (basigin; EMMPRIN), hyaluronan, and hyaluronan receptors (e.g., CD44) are intimately involved in several phenomena that underlie malignancy. A major avenue whereby they influence tumor progression is most likely their role in the characteristics of cancer stem cells (CSCs), subpopulations of tumor cells that exhibit chemoresistance, invasiveness, and potent tumorigenicity. Both CD147 and hyaluronan have been strongly implicated in chemoresistance and invasiveness, and may be drivers of CSC characteristics, since current evidence indicates that both are involved in epithelial-mesenchymal transition, a crucial process in the acquisition of CSC properties. Hyaluronan is a prominent constituent of the tumor microenvironment whose interactions with cell surface receptors influence several signaling pathways that lead to chemoresistance and invasiveness. CD147 is an integral plasma membrane glycoprotein of the Ig superfamily and cofactor in assembly and activity of monocarboxylate transporters (MCTs). CD147 stimulates hyaluronan synthesis and interaction of hyaluronan with its receptors, in particular CD44 and LYVE-1, which in turn result in activation of multiprotein complexes containing members of the membrane-type matrix metalloproteinase, receptor tyrosine kinase, ABC drug transporter, or MCT families within lipid raft domains. Multivalent hyaluronan-receptor interactions are essential for formation or stabilization of these lipid raft complexes and for downstream signaling pathways or transporter activities. We conclude that stimulation of hyaluronan-receptor interactions by CD147 and the consequent activities of these complexes may be critical to the properties of CSCs and their role in malignancy. Anat Rec, 303:1573Rec, 303: -1583Rec, 303: , 2020

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The Role of CD44 in Glucose Metabolism in Prostatic Small Cell Neuroendocrine Carcinoma

Cited by 40 publications

References 32 publications

Corilagin sensitizes epithelial ovarian cancer to chemotherapy by inhibiting Snail-glycolysis pathways

Corilagin sensitizes epithelial ovarian cancer to chemotherapy by inhibiting Snail-glycolysis pathways

CD44: A Multifaceted Molecule in Cancer Progression

The CD147‐HYALURONAN Axis in Cancer

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