The E3 ubiquitin ligase Cbl-b inhibits tumor growth in multidrug-resistant gastric and breast cancer cells

Che, Xiangyu; Zhang, Y; Qu, Xiujuan; Guo, Tao; Ma, Yanju; Li, C; Fan, Yibo; Hou, Kezuo; Cai, Yingchun; Yu, Rong; Zhang, Hongxing; He, X; Wu, Hao; Liu, Yunpeng; Xu, L

doi:10.4149/neo_2017_610

Cited by 12 publications

(8 citation statements)

References 25 publications

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“…As consistent findings in lung and gastric cancers, suppression of cell proliferation was applied by Cbl‐b through ubiquitination of the EGFR pathway [154]. Similarly, inhibition of tumor cell proliferation by Cbl‐b was also shown in breast cancers [155]. Of interest, it was shown in a report [155] that the positive expression of Cbl‐b can be considered an appropriate prognostic predictor in breast cancer, mainly in cases with lymph node metastasis and stages II–III.…”

Section: Cbl‐b In Immune‐related Diseasessupporting

confidence: 61%

“…Similarly, inhibition of tumor cell proliferation by Cbl‐b was also shown in breast cancers [155]. Of interest, it was shown in a report [155] that the positive expression of Cbl‐b can be considered an appropriate prognostic predictor in breast cancer, mainly in cases with lymph node metastasis and stages II–III.…”

Section: Cbl‐b In Immune‐related Diseasesmentioning

confidence: 96%

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E3 ubiquitin ligase Casitas B lineage lymphoma-b and its potential therapeutic implications for immunotherapy

Jafari

Mousavi

Shahbaz

et al. 2021

Clinical and Experimental Immunology

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Summary The distinction of self from non‐self is crucial to prevent autoreactivity and ensure protection from infectious agents and tumors. Maintaining the balance between immunity and tolerance of immune cells is strongly controlled by several sophisticated regulatory mechanisms of the immune system. Among these, the E3 ligase ubiquitin Casitas B cell lymphoma‐b (Cbl‐b) is a newly identified component in the ubiquitin‐dependent protein degradation system, which is thought to be an important negative regulator of immune cells. An update on the current knowledge and new concepts of the relevant immune homeostasis program co‐ordinated by Cbl‐b in different cell populations could pave the way for future immunomodulatory therapies of various diseases, such as autoimmune and allergic diseases, infections, cancers and other immunopathological conditions. In the present review, the latest findings are comprehensively summarized on the molecular structural basis of Cbl‐b and the suppressive signaling mechanisms of Cbl‐b in physiological and pathological immune responses, as well as its emerging potential therapeutic implications for immunotherapy in animal models and human diseases.

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Section: Cbl‐b In Immune‐related Diseasessupporting

confidence: 61%

Section: Cbl‐b In Immune‐related Diseasesmentioning

confidence: 96%

E3 ubiquitin ligase Casitas B lineage lymphoma-b and its potential therapeutic implications for immunotherapy

Jafari

Mousavi

Shahbaz

et al. 2021

Clinical and Experimental Immunology

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“…We have found that Cbl-b could inhibit cell proliferation by ubiquitinating the survival signal of the epidermal growth factor receptor (EGFR) pathway in lung (19,20) and gastric cancer cells (13,21,22). Also, previous studies showed that Cbl-b could inhibit tumor growth in some breast cancer cells (6,23). However, in other tumor types Cbl-b may promote the migration and proliferation of cancer cells.…”

Section: Discussionmentioning

confidence: 99%

The E3 Ubiquitin Ligase Cbl-b Predicts Favorable Prognosis in Breast Cancer

Liu

Teng

et al. 2020

Front. Oncol.

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Background: Casitas B-lineage lymphoma proto-oncogene-b (Cbl-b) is an E3 ubiquitin-protein ligase and a signal-transducing adaptor protein involved in the development and progression of cancer. Despite the known functions of Cbl-b, its role in breast cancer remains unclear. The aim of this study is to explore the prognostic value of Cbl-b in breast cancer. Methods: Cbl-b expression was analyzed by immunohistochemistry in 292 breast cancer patients from the First Hospital of China Medical University between 1999 and 2008. Kaplan-Meier curve and Cox proportional hazards regression were used to analyze the independent prognostic factors for overall survival (OS) and disease-free survival (DFS). Nomogram was constructed based on these prognostic factors. Results: Cbl-b expression was detected in 54.1% (158/292) breast cancer tissue samples. Cbl-b expression was correlated with DFS (p = 0.033), but was not significantly associated with the known clinic-pathological factors in this study. Log-rank analysis indicated that Cbl-b expression was correlated with better OS (p = 0.013) and DFS (p = 0.016). Multivariate analysis showed that Cbl-b expression was an independent prognostic factor in breast cancer. The nomogram we built for predicting OS was integrated with Cbl-b expression, age, tumor size, lymph node metastasis and histological grade. Except tumor size, all the above factors and date of diagnosis were used to construct the DFS nomogram. The C-indexes of the nomograms were 0.735 and 0.678, respectively. Our new clinical model was superior to the TNM staging for prediction of OS. Conclusion: Cbl-b expression independently predicts favorable prognosis in breast cancer. Cbl-b expression, combined with other variables could be more precise clinical predictive models for predicting OS and DFS in patients with breast cancer.

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“…Cbl-b was known to have a broad spectrum of biological functions and it regulates various signaling pathways in a cell type-dependent manner (Liyasova et al, 2015;Lutz-Nicoladoni et al, 2015). Cbl-b could inhibit proliferation of multidrug-resistant gastric and breast cancer cells (Che et al, 2017), promote shikonin-induced apoptosis in lung cancer cells (Qu et al, 2015). In addition, in our previous study, we found that Cbl-b was up-regulated during bufalininducing apoptosis in gastric cancer cells via inhibition of PI3K/Akt signaling pathway (Li et al, 2009).…”

Section: Discussionmentioning

confidence: 99%

Bufalin induces protective autophagy by Cbl‐b regulating mTOR and ERK signaling pathways in gastric cancer cells

Liu

et al. 2018

Cell Biology International

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Bufalin, a natural small-molecule compound derived from the traditional Chinese medicine Chan su, has shown promising anti-cancer effects against a broad variety of cancer cells through different mechanisms. It has been reported to induce autophagy in gastric cancer cells. However, the molecular mechanism involved is not fully elucidated. In the present study, we aimed to investigate the molecular mechanism by which bufalin induce autophagy in human gastric cancer cells. We found that bufalin induced apoptosis and autophagy in gastric cancer cells, and autophagy prevented human gastric cancer cells from undergoing apoptosis. Bufalin treatment changed the expression of autophagy-related proteins. Moreover, phosphorylated Akt, mTOR, and p70S6K were all significantly decreased, while phosphorylated ERK1/2 was increased by bufalin. Pretreatment of MGC803 cells with the ERK1/2-specific inhibitor PD98059 led to the down-regulation of LC3 II. Further study showed that Cbl-b positively regulated autophagy by suppressing mTOR and enhancing ERK1/2 activation. Therefore, our data provide evidence that bufalin induces autophagy in MGC803 cells via both Akt/mTOR/p70S6K and ERK signaling pathways, and Cbl-b-mediated suppression of mTOR and activation of ERK1/2 might play an important role.

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The E3 ubiquitin ligase Cbl-b inhibits tumor growth in multidrug-resistant gastric and breast cancer cells

Cited by 12 publications

References 25 publications

E3 ubiquitin ligase Casitas B lineage lymphoma-b and its potential therapeutic implications for immunotherapy

E3 ubiquitin ligase Casitas B lineage lymphoma-b and its potential therapeutic implications for immunotherapy

The E3 Ubiquitin Ligase Cbl-b Predicts Favorable Prognosis in Breast Cancer

Bufalin induces protective autophagy by Cbl‐b regulating mTOR and ERK signaling pathways in gastric cancer cells

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