The osteopontin-CD44 axis in hepatic cancer stem cells regulates IFN signaling and HCV replication

Shirasaki, Takayoshi; Honda, Masao; Yamashita, Taro; Nio, Kouki; Shimakami, Tetsuro; Shimizu, Ryougo; Nakasyo, Saki; Murai, Kazuhisa; Shirasaki, Natsumi; Okada, Hikari; Sakai, Yoshio; Sato, Tokiharu; Suzuki, Tetsuro; Yoshioka, Katsuji

doi:10.1038/s41598-018-31421-6

Cited by 30 publications

(16 citation statements)

References 58 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These data together suggest the regulatory role of OPN in tumor glycolysis. In HCC, OPN acts through multiple adhesion receptor binding motifs including integrins and CD44 receptors to promote tumor progression and metastasis [29,37]. In this study, we revealed that αvβ3-NF-κB signaling is responsible for OPN-induced glcolysis in HCC.…”

Section: Discussionmentioning

confidence: 70%

Integrated analysis reveals critical glycolytic regulators in hepatocellular carcinoma

et al. 2020

View full text Add to dashboard Cite

Background Cancer cells primarily utilize aerobic glycolysis for energy production, a phenomenon known as the Warburg effect. Increased aerobic glycolysis supports cancer cell survival and rapid proliferation and predicts a poor prognosis in cancer patients. Methods Molecular profiles from The Cancer Genome Atlas (TCGA) cohort were used to analyze the prognostic value of glycolysis gene signature in human cancers. Gain- and loss-of-function studies were performed to key drivers implicated in hepatocellular carcinoma (HCC) glycolysis. The molecular mechanisms underlying Osteopontin (OPN)-mediated glycolysis were investigated by real-time qPCR, western blotting, immunohistochemistry, luciferase reporter assay, and xenograft and diethyl-nitrosamine (DEN)-induced HCC mouse models. Results Increased glycolysis predicts adverse clinical outcome in many types of human cancers, especially HCC. Then, we identified a handful of differentially expressed genes related to HCC glycolysis. Gain- and loss-of-function studies showed that OPN promotes, while SPP2, LECT2, SLC10A1, CYP3A4, HSD17B13, and IYD inhibit HCC cell glycolysis as revealed by glucose utilization, lactate production, and extracellular acidification ratio. These glycolysis-related genes exhibited significant tumor-promoting or tumor suppressive effect on HCC cells and these effects were glycolysis-dependent. Mechanistically, OPN enhanced HCC glycolysis by activating the αvβ3-NF-κB signaling. Genetic or pharmacological blockade of OPN-αvβ3 axis suppressed HCC glycolysis in xenograft tumor model and hepatocarcinogenesis induced by DEN. Conclusions Our findings reveal crucial determinants for controlling the Warburg metabolism in HCC cells and provide a new insight into the oncogenic roles of OPN in HCC.

show abstract

Section: Discussionmentioning

confidence: 70%

Integrated analysis reveals critical glycolytic regulators in hepatocellular carcinoma

et al. 2020

View full text Add to dashboard Cite

show abstract

“…The authors observed a significant difference compared to the EpCAM/CD44 non-CSC population, suggesting that HCV can replicate to higher levels in CSCs. As detailed above, this higher replication and/or increased production of viral proteins can induce or maintain the CSC state [212].…”

Section: Hepatitis B and C Viral Infections In Hcc Initiation And Cscmentioning

confidence: 93%

The Cancer Stem Cell in Hepatocellular Carcinoma

Schulte

López-Gil

Sáinz

et al. 2020

Cancers

View full text Add to dashboard Cite

The recognition of intra-tumoral cellular heterogeneity has given way to the concept of the cancer stem cell (CSC). According to this concept, CSCs are able to self-renew and differentiate into all of the cancer cell lineages present within the tumor, placing the CSC at the top of a hierarchical tree. The observation that these cells—in contrast to bulk tumor cells—are able to exclusively initiate new tumors, initiate metastatic spread and resist chemotherapy implies that CSCs are solely responsible for tumor recurrence and should be therapeutically targeted. Toward this end, dissecting and understanding the biology of CSCs should translate into new clinical therapeutic approaches. In this article, we review the CSC concept in cancer, with a special focus on hepatocellular carcinoma.

show abstract

“…SPP1 can interact with several integrin receptors (αvβ1,3,5, α8β1, α9β1,4 and α4β1) to regulate cell proliferation, angiogenesis, adhesion and migration (116,148). SPP1 can also signal through CD44 (149) to activate HIF-2α-induced stemness in hepatocellular carcinoma and glioblastoma cells (150,151), and Akt-mediated cell survival in mesothelioma and colorectal cancer cells (152,153). Moreover, integrin and their associated intracellular cytoskeleton mature into reinforced focal adhesions and stress fibers, respectively, to compensate for changes in ECM stiffness (Fig.…”

Section: Expression Of Mcps In Cancermentioning

confidence: 99%

The Matrix Revolution: Matricellular Proteins and Restructuring of the Cancer Microenvironment

et al. 2020

View full text Add to dashboard Cite

The extracellular matrix (ECM) surrounding cells is indispensable for regulating their behavior. The dynamics of ECM signaling are tightly controlled throughout growth and development. During tissue remodeling, matricellular proteins (MCPs) are secreted into the ECM. These factors do not serve classical structural roles, but rather regulate matrix proteins and cell-matrix interactions to influence normal cellular functions. In the tumor microenvironment, it is becoming increasingly clear that aberrantly expressed MCPs can support multiple hallmarks of carcinogenesis by interacting with various cellular components that are coupled to an array of downstream signals. Moreover, MCPs also reorganize the biomechanical properties of the ECM to accommodate metastasis and tumor colonization. This realization is stimulating new research on MCPs as reliable and accessible biomarkers in cancer, as well as effective and selective therapeutic targets. Research.

show abstract

The osteopontin-CD44 axis in hepatic cancer stem cells regulates IFN signaling and HCV replication

Cited by 30 publications

References 58 publications

Integrated analysis reveals critical glycolytic regulators in hepatocellular carcinoma

Integrated analysis reveals critical glycolytic regulators in hepatocellular carcinoma

The Cancer Stem Cell in Hepatocellular Carcinoma

The Matrix Revolution: Matricellular Proteins and Restructuring of the Cancer Microenvironment

Contact Info

Product

Resources

About