E3 Ubiquitin Ligase Cbl-b Prevents Tumor Metastasis by Maintaining the Epithelial Phenotype in Multiple Drug-Resistant Gastric and Breast Cancer Cells

Xu, Ling; Zhang, Ye; Qu, Xiujuan; Che, Xiaofang; Guo, Tianshu; Cai, Ying; Li, Aodi; Li, Danni; Li, Ce; Wen, Ti; Fan, Yibo; Hou, Kezuo; Ma, Yanju; Hu, Xuejun; Liu, Yunpeng

doi:10.1016/j.neo.2017.01.011

Cited by 36 publications

(32 citation statements)

References 28 publications

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“…In confirmation of this notion, in silico analysis maps here identified CD81 network proteins to cellular movement pathways. Notably, expression of the CD81 interactor and HCV entry facilitator CBLB is altered in gastric and breast tumor tissue and CBLB regulates cell migration and epidermal to mesenchymal transition (EMT) through EGFR degradation [43]. This in line with recent reports that HCV entry facilitators like E cadherin can contribute to EMT [53].…”

Section: The Cd81 Network Protein Cblb As Virus Entry Facilitatorsupporting

confidence: 64%

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Hepatitis C virus enters liver cells using the CD81 receptor complex proteins calpain-5 and CBLB

et al. 2018

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Hepatitis C virus (HCV) and the malaria parasite Plasmodium use the membrane protein CD81 to invade human liver cells. Here we mapped 33 host protein interactions of CD81 in primary human liver and hepatoma cells using high-resolution quantitative proteomics. In the CD81 protein network, we identified five proteins which are HCV entry factors or facilitators including epidermal growth factor receptor (EGFR). Notably, we discovered calpain-5 (CAPN5) and the ubiquitin ligase Casitas B-lineage lymphoma proto-oncogene B (CBLB) to form a complex with CD81 and support HCV entry. CAPN5 and CBLB were required for a post-binding and pre-replication step in the HCV life cycle. Knockout of CAPN5 and CBLB reduced susceptibility to all tested HCV genotypes, but not to other enveloped viruses such as vesicular stomatitis virus and human coronavirus. Furthermore, Plasmodium sporozoites relied on a distinct set of CD81 interaction partners for liver cell entry. Our findings reveal a comprehensive CD81 network in human liver cells and show that HCV and Plasmodium highjack selective CD81 interactions, including CAPN5 and CBLB for HCV, to invade cells.

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Section: The Cd81 Network Protein Cblb As Virus Entry Facilitatorsupporting

confidence: 64%

“…The here reported HCV host factor CBLB is an E3-ubiquitin ligase, which functions together with CBL [42]. CBLB and CBL regulate EGFR endocytosis by ubiquitination of the cytosolic receptor domains [43,44]. Notably, EGFR and CBL are known HCV entry facilitators [14,29].…”

Section: The Cd81 Network Protein Cblb As Virus Entry Facilitatormentioning

confidence: 80%

Hepatitis C virus enters liver cells using the CD81 receptor complex proteins calpain-5 and CBLB

et al. 2018

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“…Nevertheless, several studies have demonstrated EMT-independent ZEB1-driven chemoresistance. For instance, EMT by itself was considered as an important process contributing to metastasis formation, but not to the limited sensitivity of multiple drug-resistant gastric and breast cancer cell models (Xu et al, 2017). Notably, human lung carcinoma cells resistant to docetaxel possessed significantly increased expression of ZEB1, while other transcriptional factors associated with EMT, including Snail, Twist, and Slug, were not deregulated (Ren J. et al, 2013).…”

Section: Interplay Between Micrornas Zeb1 and Dna Damage Responsementioning

confidence: 99%

ZEB1: A Critical Regulator of Cell Plasticity, DNA Damage Response, and Therapy Resistance

Drápela

Bouchal

Jolly

et al. 2020

Front. Mol. Biosci.

130

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The predominant way in which conventional chemotherapy kills rapidly proliferating cancer cells is the induction of DNA damage. However, chemoresistance remains the main obstacle to therapy effectivity. An increasing number of studies suggest that epithelial-to-mesenchymal transition (EMT) represents a critical process affecting the sensitivity of cancer cells to chemotherapy. Zinc finger E-box binding homeobox 1 (ZEB1) is a prime element of a network of transcription factors controlling EMT and has been identified as an important molecule in the regulation of DNA damage, cancer cell differentiation, and metastasis. Recent studies have considered upregulation of ZEB1 as a potential modulator of chemoresistance. It has been hypothesized that cancer cells undergoing EMT acquire unique properties that resemble those of cancer stem cells (CSCs). These stem-like cells manifest enhanced DNA damage response (DDR) and DNA repair capacity, self-renewal, or chemoresistance. In contrast, functional experiments have shown that ZEB1 induces chemoresistance regardless of whether other EMT-related changes occur. ZEB1 has also been identified as an important regulator of DDR by the formation of a ZEB1/p300/PCAF complex and direct interaction with ATM kinase, which has been linked to radioresistance. Moreover, ATM can directly phosphorylate ZEB1 and enhance its stability. Downregulation of ZEB1 has also been shown to reduce the abundance of CHK1, an effector kinase of DDR activated by ATR, and to induce its ubiquitin-dependent degradation. In this perspective, we focus on the role of ZEB1 in the regulation of DDR and describe the mechanisms of ZEB1-dependent chemoresistance.

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“…qRT-PCR was performed according to our previously reported method [19]. The relative expression of mRNA was calculated via the comparative cycle threshold method, and the expression of 18S was used as reference.…”

Section: Methodsmentioning

confidence: 99%

“…Protein was extracted from the cells and quantified as described previously [18, 19]. Equal amounts of protein were separated by electrophoresis on sodium dodecyl sulfate polyacrylamide gel electrophoresis gels, then transferred to polyvinylidene fluoride membranes.…”

Section: Methodsmentioning

confidence: 99%

Limb-Bud and Heart Attenuates Growth and Invasion of Human Lung Adenocarcinoma Cells and Predicts Survival Outcome

Deng

Wang

et al. 2018

Cell Physiol Biochem

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Background/Aims: The transcription cofactor limb-bud and heart (LBH) is involved in embryonic development. However, its role in human lung cancer, especially lung adenocarcinoma (LUAD), remains unclear. Methods: A public database and tissue microarray (TMA) were used to compare differences in LBH expression and its relationship with clinical characteristics. Tissue from an additional 70 LUAD patients with follow-up records was used to explore the correlation of LBH expression with prognosis. Cellular and molecular studies validated the role of LBH in LUAD growth and invasion. Results: LBH was significantly down-regulated in lung cancer tissue samples and was correlated with the prognosis and clinical characteristics of lung cancer patients based on a public database and TMA. Survival analysis revealed that LBH-negative expression was associated with poor overall survival of LUAD patients (P = 0.021). Cox regression analysis showed that LBH expression status was a favorable independent prognostic factor (hazard ratio = 0.120, 95% confidence interval = 0.016–0.894, P = 0.039). LBH knockdown accelerated LUAD cell proliferation, migration, and invasion. Furthermore, bioinformatics analysis indicated that LBH was significantly related to the cell adhesion pathway. Western blot analysis confirmed that LBH could regulate the expression of integrin family members (integrin-α1, integrin-α2, integrin-α4, integrin-αv, and integrin-β4). Conclusion: Our data suggest that LBH plays an important role in lung cancer. Importantly, LBH is an independent prognostic factor in LUAD and can attenuate cell growth and invasion. LBH may be a potential prognostic biomarker in LUAD patients.

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E3 Ubiquitin Ligase Cbl-b Prevents Tumor Metastasis by Maintaining the Epithelial Phenotype in Multiple Drug-Resistant Gastric and Breast Cancer Cells

Cited by 36 publications

References 28 publications

Hepatitis C virus enters liver cells using the CD81 receptor complex proteins calpain-5 and CBLB

Hepatitis C virus enters liver cells using the CD81 receptor complex proteins calpain-5 and CBLB

ZEB1: A Critical Regulator of Cell Plasticity, DNA Damage Response, and Therapy Resistance

Limb-Bud and Heart Attenuates Growth and Invasion of Human Lung Adenocarcinoma Cells and Predicts Survival Outcome

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