EGFR-mediated interleukin enhancer-binding factor 3 contributes to formation and survival of cancer stem-like tumorspheres as a therapeutic target against EGFR-positive non-small cell lung cancer

Cheng, Chun; Chou, Kuei Fang; Wu, Cheng Wen; Su, Nai Wen; Peng, Cheng‐Liang; Su, Ying; Chang, Jungshan; Ho, Ai Sheng; Lin, Huan; Chen, Caleb Gon Shen; Yang, Bi Ling; Chang, Yu Cheng; Chiang, Ya Wen; Lim, Ken‐Hong; Chang, Yi

doi:10.1016/j.lungcan.2017.12.017

Cited by 23 publications

(30 citation statements)

References 52 publications

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“…19 In recent years, for advanced and recurrent lung adenocarcinoma, molecular targeted therapy and immunotherapy have improved the clinical prognosis of patients to some extent. [20][21][22][23][24][25] Yet, the effect of oncogene on the tumorigeneses of lung adenocarcinoma and resistance mechanism are still not be fully elucidated. [26][27][28] At the same time, patients and society bear high medical and health costs.…”

Section: Discussionmentioning

confidence: 99%

<p>Lamin B1 Overexpresses in Lung Adenocarcinoma and Promotes Proliferation in Lung Cancer Cells via AKT Pathway</p>

Li¹,

Li²,

Li³

et al. 2020

OTT

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These authors contributed equally to this workPurpose: This study aims to investigate the biological effect and molecular mechanism of Lamin B1(LMNB1) in lung cancer cells and its significance for the prognosis of lung adenocarcinoma(LUAD) patients. Methods: In this study, Bioinformatics was performed to analyze the expression at mRNA level and prognosis effect of LMNB1 in LUAD from TCGA dataset. The immunohistochemistry(IHC) assay was conducted to analyzed the expression of LMNB1 at the protein level in LUAD tissues. The correlation between the expression of LMNB1 and the clinical factors in patients with LUAD was analyzed. Next, LMNB1 transfected into LUAD cell lines (A549 and PC-9) which was proved by Western blot. CCK8 assay, cloning formation assay, and xenograft assay were conducted to explore the effect and mechanism of LMNB1 on the proliferation of LUAD cell lines in vitro and in vivo. Results:The results of the present study demonstrated that LMNB1 was highly expressed in LUAD tissues and related to tumor stage. High LMNB1 expression was related with more advanced clinicopathological factors such as low degree of differentiation (P=0.02), large tumor size (P<0.01), lymph node metastasis (P<0.01) and higher tumor stage (P<0.01). After knocking down LMNB1, the cell growth rate (P<0.01) and the number of colonies (P<0.01) were significantly reduced, and the level of the proliferating marker Ki67 (P<0.01) was significantly decreased. At the same time, in vivo experiments showed that the tumor volume and tumor of the mice were significantly reduced (P<0.01). Moreover, we found that knockdown LMNB1 can inhibit the proliferation of lung cancer cells by inhibiting AKT phosphorylation by Western blot. Conclusion: In summary, LMNB1 play an of vital roles in the growth of LUAD cells, highlighting its potential as a therapeutic target for the treatment of LUAD patients.

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Section: Discussionmentioning

confidence: 99%

<p>Lamin B1 Overexpresses in Lung Adenocarcinoma and Promotes Proliferation in Lung Cancer Cells via AKT Pathway</p>

Li¹,

Li²,

Li³

et al. 2020

OTT

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“…Based on our collective findings, we propose that YM155 and afatinib could potentially enhance each other's efficacy in TNBC. Interestingly, YM155 has been shown to reduce EGFR expression and tumor cell proliferation and survival in pancreatic cancer 81 as well as EGFR-positive non-small cell lung cancer, in which YM155 was found to be synergistic with afatinib 82 and other EGFR inhibitors 83 , to reverse resistance to the EGFR inhibitor erlotinib in EGFR-mutant lung cancer 84 , and to inhibit EGFR autophosphorylation which promotes lung cancer stemness 85 . The EGFR inhibitor lapatinib was also found to enhance the efficacy of YM155 in neuroblastoma by inhibiting drug efflux through the ABCB1 transporter 86 .…”

Section: Scientific Reports |mentioning

confidence: 99%

Identification of synergistic drug combinations using breast cancer patient-derived xenografts

Turner

Alzubi

Harrell

2020

Sci Rep

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Compared with other breast cancer subtypes, triple-negative breast cancer (TNBC) is associated with relatively poor outcomes due to its metastatic propensity, frequent failure to respond to chemotherapy, and lack of alternative, targeted treatment options, despite decades of major research efforts. Our studies sought to identify promising targeted therapeutic candidates for TNBC through in vitro screening of 1,363 drugs in patient-derived xenograft (PDX) models. Using this approach, we generated a dataset that can be used to assess and compare responses of various breast cancer PDXs to many different drugs. Through a series of further drug screening assays and two-drug combination testing, we identified that the combination of afatinib (epidermal growth factor receptor (EGFR) inhibitor) and YM155 (inhibitor of baculoviral inhibitor of apoptosis repeat-containing 5 (BIRC5; survivin) expression) is synergistically cytotoxic across multiple models of basal-like TNBC and reduces PDX mammary tumor growth in vivo. We found that YM155 reduces EGFR expression in TNBC cells, shedding light on its potential mechanism of synergism with afatinib. Both EGFR and BIRC5 are highly expressed in basallike PDXs, cell lines, and patients, and high expression of both genes reduces metastasis-free survival, suggesting that co-targeting of these proteins holds promise for potential clinical success in TNBC. therefore suitable models for studying tumor biology and drug response, both in vivo and ex vivo/in vitro [22][23][24][25][26][27][28][29][30][31][32][33][34][35] . Using this approach, we have generated a dataset that can be used to quickly assess and compare responses of breast cancer PDXs of varying subtypes to many different drugs, most of which are approved by the U.S. Food and Drug Administration (FDA) for various cancer or non-cancer indications. From these data, we identified 176 drugs that were consistently effective across four basal-like TNBC PDXs, encompassing a wide variety of molecular targets and mechanisms of action. Several of these drugs have shown promising efficacy in TNBC and other solid tumors, however it is likely that incorporation into combination regimens is needed to maximize their efficacy and thus their likelihood of clinical success. Through a series of in vitro drug response assays, we selected four drugs to test in various two-drug combinations: carfilzomib (proteasome inhibitor), afatinib (epidermal growth factor receptor (EGFR) inhibitor), and YM155 (inhibitor of baculoviral inhibitor of apoptosis repeat-containing 5 (BIRC5; survivin) expression), along with carboplatin, a chemotherapeutic that is part of the current standard-of-care for TNBC and that we have previously tested in several PDXs 36 . Of the six drug combinations tested, we found that the combination of afatinib and YM155 was synergistically cytotoxic across four basal-like TNBC PDXs, and this drug combination significantly reduced PDX mammary tumor growth in vivo, without observable toxicity. Notably, the genes encoding the targets of ...

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“…Furthermore, compared with early-stage or well-differentiated ovarian cancer, the expression level of ILF3 was increased in late-stage or poorly-differentiated ovarian cancer (17). It has also been reported that ILF3 sustains the epidermal growth factor receptor-mediated signaling pathway in NSCLC, indicating that ILF3 may serve an important role in the occurrence of cancer (18).…”

Section: High Expression Of Interleukin-enhancer Binding Factor 3 Prementioning

confidence: 86%

“…Consequently, ILF3 participates in various cellular biological processes, including cell cycle regulation, DNA metabolism, transcription, translation, mRNA stability, microRNA expression and circular RNA (circRNA) regulation (8)(9)(10)(11)(12)(13). Moreover, ILF3 has been linked to the occurrence and progression of various malignant tumors (14)(15)(16)(17)(18). For example, ILF3 has been shown to contribute to the occurrence of breast cancer by maintaining the expression of the…”

Section: Introductionmentioning

confidence: 99%

High expression of interleukin‑enhancer binding factor 3 predicts poor prognosis in patients with lung adenocarcinoma

Zhang

Hua

et al. 2020

Oncol Lett

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Interleukin-enhancer binding factor 3 (ILF3) is a double-stranded RNA-binding protein that has been reported to contribute to the occurrence and progression of various malignant tumors. The aim of the present study was to evaluate the prognostic value of ILF3 and to apply this knowledge to avoid excessive medical treatment in patients with lung adenocarcinoma (LUAD). ILF3 expression in a discovery set consisting of tumor and peri-tumor tissue microarrays was analyzed using immunohistochemical methods. The mRNA level of ILF3 was subsequently analyzed in a validation set downloaded from The Cancer Genome Atlas. The Kaplan-Meier method, univariate and multivariate Cox analyses, decision curve analysis and nomogram models were used to evaluate the prognostic value of ILF3. ILF3 expression was upregulated in tumor tissues compared with peri-tumor tissues and was negatively associated with the overall survival time of patients with LUAD in the discovery and validation sets. Moreover, ILF3 expression was used for risk stratifica-tion in patients with tumor-node-metastasis stages II-IV and poor-to-moderate tumor differentiation. ILF3 expression was identified as an independent predictor of adverse prognosis for patients with LUAD in the discovery and validation sets. Finally, nomogram models for the 3-and 5 year survival time of patients with LUAD revealed that ILF3 expression may be used to improve the predictive accuracy of the prognosis and to avoid excessive medical treatment for certain patients with the disease. Overall, the data obtained in the current study revealed that high ILF3 expression was associated with poor prognosis, and demonstrated that ILF3, as a potential independent risk factor, may improve the hierarchical postoperative management of patients with LUAD.

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EGFR-mediated interleukin enhancer-binding factor 3 contributes to formation and survival of cancer stem-like tumorspheres as a therapeutic target against EGFR-positive non-small cell lung cancer

Cited by 23 publications

References 52 publications

<p>Lamin B1 Overexpresses in Lung Adenocarcinoma and Promotes Proliferation in Lung Cancer Cells via AKT Pathway</p>

<p>Lamin B1 Overexpresses in Lung Adenocarcinoma and Promotes Proliferation in Lung Cancer Cells via AKT Pathway</p>

Identification of synergistic drug combinations using breast cancer patient-derived xenografts

High expression of interleukin‑enhancer binding factor 3 predicts poor prognosis in patients with lung adenocarcinoma

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