Aberrant expression of cancer stem cell markers (CD44, CD90, and CD133) contributes to disease progression and reduced survival in hepatoblastoma patients: 4-year survival data

Bahnassy, Abeer A.; Fawzy, Mohamed; El-Wakil, Mohamed; Zekri, Abdel‐Rahman N.; Abdel-Sayed, Ahmed; Sheta, Marwa

doi:10.1016/j.trsl.2014.07.009

Cited by 36 publications

(28 citation statements)

References 27 publications

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“…This is particularly relevant in the context of the role of CSCs in therapeutic response and disease course and prognosis. In fact, it was recently shown that aberrantly expressed CD90 and CD133 are strongly associated with reduced sensitivity to anticancer therapy, and contribute to disease progression and poor survival rates (overall survival and disease-free survival) in patients with hepatoblastoma [32], which is consistent with the demonstrated therapeutic success of targeting the CD90/β3 integrin/AMPK/CD133 signaling axis in liver cancer reported by Chen WC et al [20], and concordant with current knowledge of the pluripotent/stemness-defining role of CD133 and CD90 in HCC [25].…”

Section: Discussionmentioning

confidence: 99%

Targeting the Epigenetic Non-Coding RNA MALAT1/Wnt Signaling Axis as a Therapeutic Approach to Suppress Stemness and Metastasis in Hepatocellular Carcinoma

Chang

Bamodu

Ong

et al. 2020

Cells

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Background: With recorded under-performance of current standard therapeutic strategies as highlighted by high rates of post-treatment (resection or local ablation) recurrence, resistance to chemotherapy, poor overall survival, and an increasing global incidence, hepatocellular carcinoma (HCC) constitutes a medical challenge. Accumulating evidence implicates the presence of HCC stem cells (HCC-SCs) in HCC development, drug-resistance, recurrence, and progression. Therefore, treatment strategies targeting both HCC-SCs and non-CSCs are essential. Methods: Recently, there has been an increasing suggestion of MALAT1 oncogenic activity in HCC; however, its role in HCC stemness remains unexplored. Herein, we investigated the probable role of MALAT1 in the SCs-like phenotype of HCC and explored likely molecular mechanisms by which MALAT1 modulates HCC-SCs-like and metastatic phenotypes. Results: We showed that relative to normal, cirrhotic, or dysplastic liver conditions, MALAT1 was aberrantly expressed in HCC, similar to its overexpression in Huh7, Mahlavu, and SK-Hep1 HCC cells lines, compared to the normal liver cell line THLE-2. We also demonstrated a positive correlation between MALAT1 expression and poor cell differentiation status in HCC using RNAscope. Interestingly, we demonstrated that shRNA-mediated silencing of MALAT1 concomitantly downregulated the expression levels of β-catenin, Stat3, c-Myc, CK19, vimentin, and Twist1 proteins, inhibited HCC oncogenicity, and significantly suppressed the HCC-SCs-related dye-effluxing potential of HCC cells and reduced their ALDH-1 activity, partially due to inhibited MALAT1-β-catenin interaction. Additionally, using TOP/FOP (TCL/LEF-Firefly luciferase) Flash, RT-PCR, and western blot assays, we showed that silencing MALAT1 downregulates β-catenin expression, dysregulates the canonical Wnt signaling pathway, and consequently attenuates HCC tumorsphere formation efficiency, with concurrent reduction in CD133+ and CD90+ HCC cell population, and inhibits tumor growth in SK-Hep1-bearing mice. Conclusions: Taken together, our data indicate that MALAT1/Wnt is a targetable molecular candidate, and the therapeutic targeting of MALAT1/Wnt may constitute a novel promising anticancer strategy for HCC treatment.

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Section: Discussionmentioning

confidence: 99%

Targeting the Epigenetic Non-Coding RNA MALAT1/Wnt Signaling Axis as a Therapeutic Approach to Suppress Stemness and Metastasis in Hepatocellular Carcinoma

Chang

Bamodu

Ong

et al. 2020

Cells

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“…For example, a CD44v3-10 isoform (variable exons 3-10) has been demonstrated to associate with and stabilize MDR1 in prostate cancer [41]. Many clinical studies have demonstrated that CD44 expression is correlated with poor prognosis and poor response to treatment, such as CD44 expression in hepatoblastoma, in gastric cancer, in chondrosarcoma and breast cancer [42][43][44][45]. Continued meta-analysis The structure of the cytoplasmic tail that its length is controlled by the inclusion of exon 18.…”

Section: Expression Profile Of Cd44 In Different Cellsmentioning

confidence: 99%

Hyaluronic acid targeting of CD44 for cancer therapy: from receptor biology to nanomedicine

Mattheolabakis

Milane

Singh

et al. 2015

Journal of Drug Targeting

474

310

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Cluster of differentiation-44 (CD44) is a ubiquitously present glycoprotein on the surface of mammalian cells that plays a significant role in a number of biological functions. Since the discovery that the receptor is over-expressed in a variety of solid tumors, such as pancreatic, breast and lung cancer, many studies have focused on methods for targeting CD44 in an attempt to improve drug delivery and discrimination between healthy and malignant tissue, while reducing residual toxicity and off-target accumulation. In this review, we describe CD44 receptor biology and its involvement in the different stages of tumor growth and metastasis, as well as methods currently used for targeting the receptor. Hyaluronic acid, the primary CD44 binding molecule, has proved a significant ally in developing nanocarriers that demonstrate preferential tumor accumulation and increased cell uptake. We outline a number of research approaches from the current literature that take advantage of hyaluronic acid's targeting ability and describe the possible advantages for each approach. The value of CD44 targeting can be easily appreciated from the number of different approaches that have reached clinical trials.

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“…1b). In the embryonal tumor hepatoblastoma which occurs in young children, increased co-expression of CD90 with CD44 and CD133 correlated with the advanced stage of the disease and associated with poor prognosis and survival [76].…”

Section: Cd90 As Marker For Malignant Cancer Cellsmentioning

confidence: 99%

“…In gastric cancer and differentiated AML subtypes, CD90 could be a marker to identify cancer stem cells as CD90 expression was high in cancer stem cells that expressed self-renewal or drug-resistance genes [9,94,95]. CD90 expression has been associated with poor survival in hepatocellular carcinoma [10,66,68,73], hepatoblastoma [76], and lung cancer [12,79,82]. Particularly, Cheng et al showed that exogenous overexpression of CD90 resulted in Cyclin D1 upregulation, E-cadherin downregulation [68] directly linking CD90 to cancer progression and metastasis in hepatocarcinoma.…”

Section: Expression In Cancer-associated Stromal Cellsmentioning

confidence: 99%

Multiple roles of CD90 in cancer

et al. 2016

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THY1 (CD90) is a 25-37-kDa heavily N-glycosylated, glycophosphatidylinositol (GPI) anchored cell surface protein. It is usually expressed on thymocytes, mesenchymal stem cells, hematopoietic stem cells, natural killer cells, neurons, endothelial cells, renal glomerular mesangial cells, follicular dendritic cells, fibroblasts, and myofibroblasts. It has been found to regulate cell adhesion, migration, apoptosis, axon growth, cell-cell and cell-matrix interactions, T-cell activation, and fibrosis. Several reports have shown that CD90 has an important role in cancer in regulating cancer cell proliferation, metastasis, and angiogenesis. There are also evidences that CD90 is an important prognostic marker in many cancers. Consequently, therapies that target CD90 have great promise in treating many cancers. However, several studies also indicate a contradictory role for CD90, where it acts as a tumor suppressor. In this review, we summarize the expression, function of CD90 in different cancers and its possible use as a biomarker or a therapeutic target in cancer. The challenges and future prospects for the use of CD90 for clinical applications are also discussed in this review.

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Aberrant expression of cancer stem cell markers (CD44, CD90, and CD133) contributes to disease progression and reduced survival in hepatoblastoma patients: 4-year survival data

Cited by 36 publications

References 27 publications

Targeting the Epigenetic Non-Coding RNA MALAT1/Wnt Signaling Axis as a Therapeutic Approach to Suppress Stemness and Metastasis in Hepatocellular Carcinoma

Targeting the Epigenetic Non-Coding RNA MALAT1/Wnt Signaling Axis as a Therapeutic Approach to Suppress Stemness and Metastasis in Hepatocellular Carcinoma

Hyaluronic acid targeting of CD44 for cancer therapy: from receptor biology to nanomedicine

Multiple roles of CD90 in cancer

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