Ling Zhi-8 reduces lung cancer mobility and metastasis through disruption of focal adhesion and induction of MDM2-mediated Slug degradation

Lin, Tsai-Yun; Hsu, Hsien Yeh

doi:10.1016/j.canlet.2016.03.018

Cited by 70 publications

(40 citation statements)

References 34 publications

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“…The Lewis lung carcinoma cell line (LLC1) was purchased from BCRC (Hsinchu, Taiwan). All cells were cultured as previously described …”

Section: Methodsmentioning

confidence: 99%

“…All cells were cultured as previously described. 2,6,23 Preparation of the recombinant Ling Zhi-8 (rLZ-8) protein…”

Section: Cell Linesmentioning

confidence: 99%

“…LZ‐8 has excellent thermal and acid stability, and it shares biological functions similar to other FIPs. We previously demonstrated that recombinant LZ‐8 (rLZ‐8) effectively prevented lung cancer cell proliferation and metastasis by mediating the activity of the ribosomal protein S7‐MDM2‐p53 pathway and promoting MDM2‐mediated ubiquitination‐dependent Slug degradation . However, there remains no evidence show the targeted membrane protein of rLZ‐8 on cancer cells.…”

Section: Introductionmentioning

confidence: 99%

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Induction of Cbl-dependent epidermal growth factor receptor degradation in Ling Zhi-8 suppressed lung cancer

Lin

Hsu

Sun³

et al. 2017

Int. J. Cancer

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Activating mutation of epidermal growth factor receptor (EGFR) is correlated with malignant lung tumor. In our study, we demonstrated that recombinant LZ-8 (rLZ-8), a medicinal mushroom Ganoderma lucidum protein, induced cell cycle arrest and apoptosis by downregulating the expression of wild-type and mutated EGFR and inhibiting EGFR downstream effectors, AKT and ERK1/2 in lung cancer cells. We showed that rLZ-8 effectively inhibited lung cancer progression and suppressed EGFR expression of lung tumor lesions in mouse model. Functional studies revealed that rLZ-8 reduced the amount of EGFR in cell membranes by altering EGFR localization to enhance the EGF-induced degradation of EGFR. Mechanistically, we demonstrated that rLZ-8 bound to EGFR to induce EGFR autophosphorylation at tyrosine1045 and trigger ubiquitination by inducing the formation of EGFR/Cbl complexes, resulting in the degradation of EGFR; however, Cbl-shRNA abolished rLZ-8-induced EGFR degradation. We provide the first evidence showing that rLZ-8 inhibits growth and induces apoptosis of lung cancer cells by promoting EGFR degradation. The current findings therefore suggest a novel anti-cancer function of rLZ-8 that targeting EGFR overexpression or mutation as well as EGFR-dependent processes in cancer cells.

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“…The Lewis lung carcinoma cell line (LLC1) was purchased from BCRC (Hsinchu, Taiwan). All cells were cultured as previously described …”

Section: Methodsmentioning

confidence: 99%

“…All cells were cultured as previously described. 2,6,23 Preparation of the recombinant Ling Zhi-8 (rLZ-8) protein…”

Section: Cell Linesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Induction of Cbl-dependent epidermal growth factor receptor degradation in Ling Zhi-8 suppressed lung cancer

Lin

Hsu

Sun³

et al. 2017

Int. J. Cancer

Self Cite

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show abstract

“…RNA transport coupled with translation control is a crucial mechanism to target protein expression to specific regions of a cell or an organism. Focal adhesion, which involves the subcellular structure mediating the regulatory effects of a cell in response to ECM adhesion, plays very important role in cancer metastasis through relative protein focal adhesion kinase 20,21. Together, mRNAs and proteins form large ribonucleoprotein complexes in which different factors control assembly, stability, translation, and transport of localized mRNAs 9.…”

mentioning

confidence: 99%

Proteomic analysis of the effects of cell culture density on the metastasis of breast cancer cells

Guo

Mixin

Lan

et al. 2019

Cell Biochemistry & Function

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Cancer cell progression and proliferation increase cell density, resulting in changes to the tumour site, including the microenvironment. What is not known is if increased cell density influences the aggressiveness of cancer cells, especially their proliferation, migration, and invasion capabilities. In this study, we found that dense cell culture enhances the aggressiveness of the metastatic cancer cell lines, 4T1 and ZR-75-30, by increasing their proliferation, migration, and invasion capabilities. However, a less metastatic cell line, MCF-7, did not show an increase in aggressiveness, following dense cell culture conditions. We conducted a differential proteomic analysis on 4T1 cells cultured under dense or sparse conditions and identified an increase in expression for proteins involved in migration, including focal adhesion, cytoskeletal reorganization, and transendothelial migration. In contrast, 4T1 cells grown under sparse conditions had higher expression levels for proteins involved in metabolism, including lipid and phospholipid binding, lipid and cholesterol transporter activity, and protein binding.These results suggest that the high-density tumour microenvironment can cause a change in cellular behaviour, leading towards more aggressive cancers.Significance of the study: Metastasis of cancer cells is an obstacle to the clinical treatment of cancer. We found that dense cultures made metastatic cancer cells more potent in terms of proliferation, migration, and invasion. The proteomic and bioinformatic analyses provided some valuable clues for further intensive studies about the effects of cell density on cancer cell aggressiveness, which were associated with events such as pre-mRNA splicing and RNA transport, focal adhesion and cytoskeleton reorganization, ribosome biogenesis, and transendothelial migration, or associated with proteins, such as JAM-1 and S100A11. This investigation gives us new perspectives to investigate the metastasis mechanisms related to the microenvironment of tumour sites.

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“…Interestingly, one of the major steps during EMT in cancer cells is a change in cellular focal adhesion. Indeed, EMT-associated migration and metastasis in cancer cells is induced by the disruption of focal adhesion [32]. The Wnt signaling pathway has also been identified as playing a key role in lung cancer invasion [33].…”

Section: Discussionmentioning

confidence: 99%

Benzotriazole Enhances Cell Invasive Potency in Endometrial Carcinoma Through CTBP1-Mediated Epithelial-Mesenchymal Transition

Wang

Dai

Zhou

et al. 2017

Cell Physiol Biochem

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Background/Aims: Benzotriazole (BTR) and its derivatives, such as intermediates and UV stabilizers, are important man-made organic chemicals found in everyday life that have been recently identified as environmental toxins and a threat to female reproductive health. Previous studies have shown that BTR could act as a carcinogen by mimicking estrogen. Environmental estrogen mimics could promote the initiation and development of female cancers, such as endometrial carcinoma, a type of estrogenic-sensitive malignancy. However, there is little information on the relationship between BTR and endometrial carcinoma. In this study, we aimed to demonstrate the biological function of BTR in endometrial carcinoma and explored the underlying mechanism. Methods: The CCK-8 assay was performed to detect cell viability; transwell-filter assay was used to assess cell invasion; gene microarray analysis was employed to determine gene expression patterns in response to BTR treatment; western blotting and quantitative reverse transcription polymerase chain reaction (qRT-PCR) were carried out to detect the expression levels of BTR-related genes. Results: Our data showed that BTR could induce the invasion and migration of endometrial carcinoma cells (Ishikawa and HEC-1-B). In addition, BTR increased the expression level of CTBP1, which could enhance the epithelial-mesenchymal transition (EMT) in cancer cells. Moreover, CTBP1 silencing reversed the effect of BTR on EMT progression in endometrial carcinoma cells. Conclusion: This study indicates that BTR could act as a carcinogen to promote the development of endometrial carcinoma mainly through CTBP1-mediated EMT, which deserves more attention.

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Ling Zhi-8 reduces lung cancer mobility and metastasis through disruption of focal adhesion and induction of MDM2-mediated Slug degradation

Cited by 70 publications

References 34 publications

Induction of Cbl-dependent epidermal growth factor receptor degradation in Ling Zhi-8 suppressed lung cancer

Induction of Cbl-dependent epidermal growth factor receptor degradation in Ling Zhi-8 suppressed lung cancer

Proteomic analysis of the effects of cell culture density on the metastasis of breast cancer cells

Benzotriazole Enhances Cell Invasive Potency in Endometrial Carcinoma Through CTBP1-Mediated Epithelial-Mesenchymal Transition

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