Targeting a novel cancer-driving protein (LAPTM4B-35) by a small molecule (ETS) to inhibit cancer growth and metastasis

Li, Maojin; Zhou, Ruanbao; Shan, Yi; Li, Li; Wang, Lin; Liu, Gang

doi:10.18632/oncotarget.11325

Cited by 5 publications

(4 citation statements)

References 20 publications

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“…A number of studies have shown that the proliferation of cells overexpressing LAPTM4B is closely correlated with tumor progression and metastasis [ 20 , 21 ]. In our study, increased LAPTM4B expression was strongly associated with prognosis-related features, including tumor size, TNM stage and lymph node metastasis.…”

Section: Discussionmentioning

confidence: 99%

Increased levels of LAPTM4B, VEGF and survivin are correlated with tumor progression and poor prognosis in breast cancer patients

Wang

Yue

et al. 2017

Oncotarget

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ObjectiveThis study explored the relationships among the expression of LAPTM4B, VEGF, and survivin and clinicopathological characteristics and prognosis in breast cancer patients.MethodsThe expression of these three molecules in 110 stage I-III breast cancer patients with clinicopathological and follow-up data was detected via immunohistochemistry. Kaplan-Meier and Cox proportional hazard regression analyses were performed to assess the prognostic significance of these markers in breast cancer. Moreover, expression levels of these markers were evaluated in 5 breast cell lines via Western blot analysis.ResultsLAPTM4B, VEGF, and survivin were over-expressed in breast cancer specimens and highly expressed in MDA-MB-231 cells. VEGF and nuclear survivin expression was significantly correlated with LAPTM4B expression, and high levels of all three were associated with a tumor size >2cm, TNM stage II+III and lymph node metastasis, which had worse impacts on overall survival and progression-free survival in breast cancer patients. A multivariate Cox analysis identified LAPTM4B over-expression as an independent prognostic marker in breast cancer.ConclusionsThese findings suggest that LAPTM4B, VEGF, and nuclear survivin expression are significantly correlated in breast cancer, which may be predictive of prognosis as well as effective therapeutic targets for new anticancer therapies.

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Section: Discussionmentioning

confidence: 99%

Increased levels of LAPTM4B, VEGF and survivin are correlated with tumor progression and poor prognosis in breast cancer patients

Wang

Yue

et al. 2017

Oncotarget

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“…Akt and mTOR overexpression improved the protective effects after cerebral ischemia-reperfusion injury in MCAO rats, suggesting that the activation of the PI3K/Akt/mTOR signaling pathway provides significant neuroprotective effects against cerebral ischemia-reperfusion injury. P-Akt and p-mTOR ( Li et al, 2016 ; Yang et al, 2017 ; Park et al, 2019 ; Sun et al, 2020 ) are commonly recognized as markers for activation of the PI3K/Akt/mTOR pathway. In the present study, the levels of p-AKT and p-mTOR were significantly decreased following I/R injury and were activated by TFCJ treatment.…”

Section: Discussionmentioning

confidence: 99%

Total Flavonoids of Chuju Decrease Oxidative Stress and Cell Apoptosis in Ischemic Stroke Rats: Network and Experimental Analyses

et al. 2021

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Background: Pharmacological research results showed that total flavonoids of Chuju (TFCJ) could be used to treat acute myocardial ischemia and myocardial ischemia-reperfusion injury. In this study, we explored the protective effect of TFCJ on ischemic stroke (IS) in the IS rat model. We hypothesized that TFCJ might exert its neuroprotective effects by suppressing apoptosis and oxidative stress that are closely related to PI3K/Akt/mTOR signaling pathway.Method: TFCJ (10, 20, and 40 mg/kg) was administered for 7 days. Rats (260 ± 20 g) were subjected to middle cerebral artery occlusion (MCAO) for 2 h and reperfusion for 24 h. The neuroprotective effect of TFCJ was substantiated in terms of neurological deficits, oxidative stress (superoxide dismutase, glutathione peroxidase, catalase, and malondialdehyde), pathomorphological changes (HE staining and TUNEL staining), and neurobehavioral functions in the rats. Then, we employed network pharmacology to reveal the potential mechanism of TFCJ against IS. Western blot was used to determine the levels of PI3K/AKT/mTOR pathway proteins. The expression of BCL-2, BAX, and cleaved-Caspase-3 was also measured by Western blots and RT-PCR.Results: The histopathological assessment showed that TFCJ reduced MCAO-induced brain damage. Besides, TFCJ exerted a protective role in MCAO rats by alleviating cell apoptosis and oxidative stress. Network pharmacology showed that TFCJ might be used against IS through the PI3K/AKT signaling pathway. TFCJ reduced cell apoptosis and oxidative stress by increasing the level of p-AKT and p-mTOR in MCAO rats, while the effect of TFCJ was significantly reversed when applying LY294002 (PI3k inhibitor).Conclusion: These results indicated that TFCJ might decrease oxidative stress and apoptosis that are closely related to PI3K/Akt/mTOR pathway in IS. TFCJ is a promising authentic traditional Chinese medicine for the management of IS.

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“…LAPTM4B was also associated with tumor proliferation, angiogenesis, and poor prognosis in patients with glioblastoma, which could be used as a potential novel prognostic marker of glioblastoma to improve its treatment ( 35 ). Ethylglyoxal bisthiosemicarbazon, a specific inhibitor of LAPTM4B, was found to have effective antitumor activity in HCC ( 36 ).…”

Section: Discussionmentioning

confidence: 99%

LAPTM4B promotes the progression of bladder cancer by stimulating cell proliferation and invasion

Yin

Yang

et al. 2021

Oncol Lett

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Bladder cancer is a highly metastatic tumor and one of the most common malignant tumors originating in the urinary system. Due to the complicated etiology and lack of significant early symptoms, the diagnosis and treatment of bladder cancer is difficult. Lysosome-associated transmembrane protein 4β (LAPTM4B) was reported to be involved in the development and progression of several types of tumor, however, its potential effect on the development and metastasis of bladder cancer is still unclear. Immunohistochemistry was performed to detect the protein expression level of LAPTM4B in bladder cancer tissues and short hairpin RNAs targeting LAPTM4B were transfected into bladder cancer cells to knockdown its expression. MTT and colony formation assays were performed to detect cell proliferation, while wound healing and Transwell invasion assays were performed to detect cell migration and invasion, respectively. In addition, tumor growth assays were performed to confirm the effects of LAPTM4B in mice. The present study demonstrated that LAPTM4B was associated with the prognosis of patients with bladder cancer. In addition, LAPTM4B was associated with clinical characteristics, including tumor stage and recurrence. The results further showed that LAPTM4B knockdown could suppress the proliferation of bladder cancer cell lines. In addition, the migration and invasion of T24 and 5637 cells was suppressed following LAPTM4B knockdown in vitro. The in vivo data confirmed that knockdown of LAPTM4B markedly inhibited tumor growth and metastasis in mice. In summary, the results from the present study provide strong evidence of the effects of LAPTM4B in bladder cancer progression.

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Targeting a novel cancer-driving protein (LAPTM4B-35) by a small molecule (ETS) to inhibit cancer growth and metastasis

Cited by 5 publications

References 20 publications

Increased levels of LAPTM4B, VEGF and survivin are correlated with tumor progression and poor prognosis in breast cancer patients

Increased levels of LAPTM4B, VEGF and survivin are correlated with tumor progression and poor prognosis in breast cancer patients

Total Flavonoids of Chuju Decrease Oxidative Stress and Cell Apoptosis in Ischemic Stroke Rats: Network and Experimental Analyses

LAPTM4B promotes the progression of bladder cancer by stimulating cell proliferation and invasion

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