The Significance of MMP-1 in EGFR-TKI–Resistant Lung Adenocarcinoma: Potential for Therapeutic Targeting

Saito, Ryoko; Miki, Yasuhiro; Ishida, Naoya; Inoue, Chihiro; Kobayashi, Masayuki; Hata, Shuko; Yamada-Okabe, Hisafumi; Okada, Yoshinori; Sasano, Hironobu

doi:10.3390/ijms19020609

Cited by 26 publications

(27 citation statements)

References 29 publications

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“…Weiss et al reported that MMP-1 participated in the proliferation of melanoma in coordination with TWIST1 in vitro (34). A study by Saito et al revealed that MMP-1 contributed to the migration of lung carcinoma via the mTOR signaling pathway in vitro (14). Furthermore, research by Fuhrman-Luck et al demonstrated that MMP-1 promoted prostate cancer bone metastases in a humanized in vivo bone metastasis model related to KLK4 (35).…”

Section: Discussionmentioning

confidence: 99%

“…The upregulation of MMP-1 has been revealed to be involved in the incidence or invasion of diverse cancers, including bladder (9), prostate (10), gastric (11), pancreatic (12) and melanoma (13). A recent study indicated that the significance of MMP-1 could make it a potential therapeutic target in lung adenocarcinoma (14). Some previous studies have suggested that MMP-1 may be expressed at a high level in colorectal cancer (15,16).…”

Section: Introductionmentioning

confidence: 99%

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Knockdown of MMP‑1 inhibits the progression of colorectal cancer by suppressing the PI3K/Akt/c‑myc signaling pathway and EMT

Wang

Zheng

et al. 2020

Oncol Rep

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The present study aimed to investigate the role of matrix metalloproteinase-1 (MMP-1) in the development of colorectal cancer and reveal the mechanism underlying this progression. Bioinformatics methods and a public dataset were first used to analyze MMP-1 gene expression in a public dataset. MMP-1 expression in colorectal cancer patients was assessed by immunohistochemistry; its association with clinicopathological parameters and its significance for prognosis were analyzed. Then proliferation, scratch and Transwell assays and a xenograft model were used to assess the change in malignant behavior in cells transfected with an MMP-1 shRNA. Changes involved in epithelial-mesenchymal transition (EMT) and the Akt signaling pathway were detected by western blotting. According to the results, MMP-1 expression was higher in colorectal cancer tissues than it was in matched adjacent noncancerous tissues, and its high expression was significantly related to lymphatic metastasis as well as TNM stage (P<0.05). Downregulation of MMP-1 expression inhibited the progression of colorectal cancer in vitro and in vivo. Furthermore, after the cells were stably transfected with MMP-1 shRNA, the expression of N-cadherin, vimentin and Twist1 decreased while that of E-cadherin increased. The expression of p-Akt and c-Myc also decreased. In conclusion, MMP-1 may promote malignant behavior in colorectal cancer via EMT and the Akt signaling pathway.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Knockdown of MMP‑1 inhibits the progression of colorectal cancer by suppressing the PI3K/Akt/c‑myc signaling pathway and EMT

Wang

Zheng

et al. 2020

Oncol Rep

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“…[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. Therefore, it is urgent to find effective oncogenes to guide the respiratory doctor to make accurate diagnosis and treatment for different patients.…”

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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“…Following prognosis analysis revealed that several lipid-metabolism genes may not only be diagnosis biomarkers for tumors but may also be prognosis biomarkers, such as MMP1 and HMGCS2. It has been reported that MMP1 overexpression has an important role in promoting tumor cell invasion [21] and HMGCS2 silence promoted tumor cells metastatic via Epithelial-Mesenchymal Transition (EMT) process and the activation of ERK/c-Jun signaling pathway [22]. We also revealed lipid metabolism biomarkers that were closely correlated with the tumor immune microenvironment, such as CD36.…”

Section: Discussionmentioning

confidence: 63%

Investigation of lipid metabolism dysregulation and the effects on immune microenvironments in pan-cancer using multiple omics data

Yang

et al. 2019

BMC Bioinformatics

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Background Lipid metabolism reprogramming is a hallmark for tumor which contributes to tumorigenesis and progression, but the commonality and difference of lipid metabolism among pan-cancer is not fully investigated. Increasing evidences suggest that the alterations in tumor metabolism, including metabolite abundance and accumulation of metabolic products, lead to local immunosuppression in the tumor microenvironment. An integrated analysis of lipid metabolism in cancers from different tissues using multiple omics data may provide novel insight into the understanding of tumorigenesis and progression. Results Through systematic analysis of the multiple omics data from TCGA, we found that the most-widely altered lipid metabolism pathways in pan-cancer are fatty acid metabolism, arachidonic acid metabolism, cholesterol metabolism and PPAR signaling. Gene expression profiles of fatty acid metabolism show commonalities across pan-cancer, while the alteration in cholesterol metabolism and arachidonic acid metabolism differ with tissue origin, suggesting tissue specific lipid metabolism features in different tumor types. An integrated analysis of gene expression, DNA methylation and mutations revealed factors that regulate gene expression, including the differentially methylated sites and mutations of the lipid genes, as well as mutation and differential expression of the up-stream transcription factors for the lipid metabolism pathways. Correlation analysis of the proportion of immune cells in the tumor microenvironment and the expression of lipid metabolism genes revealed immune-related differentially expressed lipid metabolic genes, indicating the potential crosstalk between lipid metabolism and immune response. Genes related to lipid metabolism and immune response that are associated with poor prognosis were discovered including HMGCS2, GPX2 and CD36, which may provide clues for tumor biomarkers or therapeutic targets. Conclusions Our study provides an integrated analysis of lipid metabolism in pan-cancer, highlights the perturbation of key metabolism processes in tumorigenesis and clarificates the regulation mechanism of abnormal lipid metabolism and effects of lipid metabolism on tumor immune microenvironment. This study also provides new clues for biomarkers or therapeutic targets of lipid metabolism in tumors. Electronic supplementary material The online version of this article (10.1186/s12859-019-2734-4) contains supplementary material, which is available to authorized users.

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The Significance of MMP-1 in EGFR-TKI–Resistant Lung Adenocarcinoma: Potential for Therapeutic Targeting

Cited by 26 publications

References 29 publications

Knockdown of MMP‑1 inhibits the progression of colorectal cancer by suppressing the PI3K/Akt/c‑myc signaling pathway and EMT

Knockdown of MMP‑1 inhibits the progression of colorectal cancer by suppressing the PI3K/Akt/c‑myc signaling pathway and EMT

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

Investigation of lipid metabolism dysregulation and the effects on immune microenvironments in pan-cancer using multiple omics data

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