Enhanced tumorigenesis and lymphatic metastasis of CD133+ hepatocarcinoma ascites syngeneic cell lines mediated by JNK signaling pathway in vitro and in vivo

Jin, Yanling; Murata, Jun; Wang, Huanxi; Hou, Zhengxin; Ma, Wei; Zhang, Jun; Wang, Bo; Huang, Yühong; Zang, Shizhu; Tang, Jianwu; Li, Lianhong

doi:10.1016/j.biopha.2013.02.006

Cited by 14 publications

(16 citation statements)

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“…Using a fold-change cutoff of >3, 2,372 differentially expressed genes were identified. Subsequent pathway analysis found many of the deregulated genes to be closely associated with JNK / AP-1 and MAPK , pathways, which have previously been shown to play a critical role in HCC pathogenesis ( Figure 6 A; Figure S4 B) ( Hagiwara et al., 2012; Jin et al., 2013 ). Deregulation of key players of the JNK pathway, including p-MKK4, JNK kinase activity, c-MYC, and p21, was subsequently validated by western blot in HCC cells with ANXA3 repressed (Huh7 and PLC8024) or overexpressed (MIHA) ( Figure 6 B).…”

Section: Resultsmentioning

confidence: 89%

ANXA3/JNK Signaling Promotes Self-Renewal and Tumor Growth, and Its Blockade Provides a Therapeutic Target for Hepatocellular Carcinoma

et al. 2015

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SummaryFrequent tumor relapse in hepatocellular carcinoma (HCC) has been commonly attributed to the presence of residual cancer stem cells (CSCs) after conventional treatments. We have previously identified and characterized CD133 to mark a specific CSC subset in HCC. In the present study, we found endogenous and secretory annexin A3 (ANXA3) to play pivotal roles in promoting cancer and stem cell-like features in CD133+ liver CSCs through a dysregulated JNK pathway. Blockade of ANXA3 with an anti-ANXA3 monoclonal antibody in vitro as well as in human HCC xenograft models resulted in a significant reduction in tumor growth and self-renewal. Clinically, ANXA3 expression in HCC patient sera closely associated with aggressive clinical features. Our results suggest that ANXA3 can serve as a novel diagnostic biomarker and that the inhibition of ANXA3 may be a viable therapeutic option for the treatment of CD133+ liver-CSC-driven HCC.

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Section: Resultsmentioning

confidence: 89%

ANXA3/JNK Signaling Promotes Self-Renewal and Tumor Growth, and Its Blockade Provides a Therapeutic Target for Hepatocellular Carcinoma

et al. 2015

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“…In addition, haplo-insufficiency of Annexin A7 expression appears to drive disease progression to cancer because the genomic instability could lead to a discrete signaling pathway to reduce expression of the other tumor suppressor genes, DNA-repair genes, or apoptosis-related genes [12]. Some work regarding Annexin A7 from our laboratory clearly showed that the Annexin A7 gene is associated with lymph node metastasis and progression of HCC [5-7,16-19]. However, the tumor suppressor mechanisms of Annexin A7 in HCC have not yet been elucidated.…”

Section: Discussionmentioning

confidence: 99%

Annexin A7 suppresses lymph node metastasis of hepatocarcinoma cells in a mouse model

et al. 2013

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BackgroundHepatocellular carcinoma (HCC) is one of the leading causes of cancer death in China. This study investigated the effects of Annexin A7 (ANXA7) on the inhibition of HCC lymph node metastasis in a mouse model.MethodsThe stable knockup and knockdown of Annexin A7-expressing HCC cells using Annexin A7 cDNA and shRNA vectors, respectively, were injected into a mouse footpad to establish primary and metastatic tumors in mice. On the 14th, 21st, and 28th days after HCC cells inoculation, the mice were sacrificed for inspection of primary and secondary tumors and immunohistochemistry of Annexin A7 expression.ResultsThe lymph node metastasis rate of the FANXA7-control group was 77%, and the lymph node metastasis rate of the FANXA7-down group was 100% (p < 0.05). In contrast, the lymph node metastasis rate of the PANXA7-up group was 0% and that of the PANXA7-control group was 36% (p < 0.05). Furthermore, immunohistochemistry experiments revealed that the subcellular localization of Annexin A7 protein in both primary and lymph node-metastasized tumors was mainly in the cytosol. In addition, the expression of the 47 kDa and 51 kDa isoforms of Annexin A7 protein changed during tumor progression.ConclusionThis study indicated that Annexin A7 expression was able to inhibit HCC lymph node metastasis, whereas knockdown of Annexin A7 expression significantly induced HCC metastasis to local lymph nodes.

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“…This theory based on the identification of metastatic features in primary tumor cells or even their transformed precursors before the initiation with the neoplastic progression. Moreover, functional genomic studies revealed that limited subsets of tumor cells within the primary lesions are programmed to metastasize to specific organs [63,64]. Thus, in the context of CSC concept, it is plausible that these limited subsets of tumor cells/subpopulations may be attributed to CSCs, and thereby have the capacity to initiate tumor formation.…”

Section: Mechanisms Of Cancer Stem-like Cells In Melanoma Progressionmentioning

confidence: 99%

Cancer Stem- Like Cells in Melanoma Progression, Resistance and Recurrence: Significance for Melanoma Treatment

Hassan¹,

A²,

Haïkel³

et al. 2014

IJST

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Human malignant melanoma is a highly aggressive tumor which demonstrates heterogeneity and a propensity to drug resistance. Despite improved treatment options, patients with advanced malignant melanoma continue have a poor prognosis as measured by progression-free and overall survival. The cancer stem-like cell (CSC) hypothesis suggests that neoplastic clones are maintained by a small fraction of cells with stem cell properties. As has been demonstrated with other tumor types, melanoma progression, resistance to chemo-and radiotherapy, and recurrence can be attributed to a small fraction of cells termed melanoma stem-like cells (MSCs). These MSCs are characterized by a distinct protein patterns and aberrant signaling pathways, which are either in a causal or consequential relationship to tumor progression, drug resistance and recurrence. This review focuses on the mechanistic role of MSCs leading to tumor progression and metastasis, resistance and recurrence. Understanding the molecular mechanisms underlying MSCs migration, invasion, resistance to standard treatments, and recurrence may help to improve current therapeutic modalities and/or pave the way for the development of new therapeutical management strategy for tumor treatment.

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Enhanced tumorigenesis and lymphatic metastasis of CD133+ hepatocarcinoma ascites syngeneic cell lines mediated by JNK signaling pathway in vitro and in vivo

Cited by 14 publications

References 42 publications

ANXA3/JNK Signaling Promotes Self-Renewal and Tumor Growth, and Its Blockade Provides a Therapeutic Target for Hepatocellular Carcinoma

ANXA3/JNK Signaling Promotes Self-Renewal and Tumor Growth, and Its Blockade Provides a Therapeutic Target for Hepatocellular Carcinoma

Annexin A7 suppresses lymph node metastasis of hepatocarcinoma cells in a mouse model

Cancer Stem- Like Cells in Melanoma Progression, Resistance and Recurrence: Significance for Melanoma Treatment

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