Antitumor effect of the integrin α4 signaling inhibitor JK273 in non-small cell lung cancer NCI-H460 cells

Lu, Thien Nhan; Ganganna, Bogonda; Pham, Thuy Trang; Vo, Anh Van; Lu, Thien Phuc; Nguyen, Huong-Giang Thi; Nguyen, My-Nuong Thi; Huynh, Phuong N.; Truong, Ngoc Tuyen; Lee, Jong-Kook

doi:10.1016/j.bbrc.2017.07.096

Cited by 4 publications

(2 citation statements)

References 13 publications

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“…It was identified by Lee J. and colleagues through a cell-based screen of small molecule libraries and has been shown to inhibit integrin α4-dependent cell migration [ 143 ]. Recently, the same group reported that this small molecule exerted a selective cytotoxic effect against non-small cell lung cancer NCI-H460 cells [ 144 ]. Further studies are warranted to determine its antitumor effect on other solid tumors, including melanoma.…”

Section: Integrins As Targets For Melanoma Therapiesmentioning

confidence: 99%

Integrins as therapeutic targets in the organ-specific metastasis of human malignant melanoma

Huang

Rofstad

2018

J Exp Clin Cancer Res

135

134

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Integrins are a large family of adhesion molecules that mediate cell-cell and cell-extracellular matrix interactions. Among the 24 integrin isoforms, many have been found to be associated with tumor angiogenesis, tumor cell migration and proliferation, and metastasis. Integrins, especially αvβ3, αvβ5 and α5β1, participate in mediating tumor angiogenesis by interacting with the vascular endothelial growth factor and angiopoietin-Tie signaling pathways. Melanoma patients have a poor prognosis when the primary tumor has generated distant metastases, and the melanoma metastatic site is an independent predictor of the survival of these patients. Different integrins on the melanoma cell surface preferentially direct circulating melanoma cells to different organs and promote the development of metastases at specific organ sites. For instance, melanoma cells expressing integrin β3 tend to metastasize to the lungs, whereas those expressing integrin β1 preferentially generate lymph node metastases. Moreover, tumor cell-derived exosomes which contain different integrins may prepare a pre-metastatic niche in specific organs and promote organ-specific metastases. Because of the important role that integrins play in tumor angiogenesis and metastasis, they have become promising targets for the treatment of advanced cancer. In this paper, we review the integrin isoforms responsible for angiogenesis and organ-specific metastasis in malignant melanoma and the inhibitors that have been considered for the future treatment of metastatic disease.

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Section: Integrins As Targets For Melanoma Therapiesmentioning

confidence: 99%

Integrins as therapeutic targets in the organ-specific metastasis of human malignant melanoma

Huang

Rofstad

2018

J Exp Clin Cancer Res

135

134

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“…Not only do these molecules have a very high correlation with CHST11 in LUAD-related cells, but they also have clinically significant poor prognoses (Figure S6). Internal signaling plays a role in the progression of LUAD [37][38][39][40]. Several studies have suggested that integrin signaling may contribute to pulmonary fibrosis by altering TGF-β expression [41].…”

Section: Discussionmentioning

confidence: 99%

The CHST11 gene is linked to lung cancer and pulmonary fibrosis

Chan

Chang

et al. 2022

The Journal of Gene Medicine

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Background The abnormal modification of chondroitin sulfate is one of the leading causes of disease, including cancer progression. During chondroitin sulfate biosynthesis, the CHST11 enzyme plays a vital role in its modification, but its role in cancer is not fully understood. Therefore, understanding the relationship between CHST11 and pulmonary‐related diseases through clinically relevant information may be useful for diagnosis or treatment. Methods A variety of pulmonary fibrosis clinical gene expression omnibus (GEO) datasets were used to assess the association between CHST11‐related manifestations and fibrosis. Multiple lung cancer‐related databases, including The Cancer Genome Atlas, GEO datasets, UCSC Xena, GEPIA2, Cbioportal and ingenuity pathway analysis were used to evaluate the clinical correlation between CHST11 and lung cancer and potential molecular mechanisms. For drug repurposing prediction, the molecules that correlated with CHST11 were subjected to the LINCS L1000 algorithm. A variety of in vitro assays were performed to evaluate the in‐silico models, including RNA and protein expression, proliferation, migration and invasion. Results Clinical analyses indicate that the levels of CHST11 are significantly elevated in cases of pulmonary‐related diseases, including fibrosis and lung cancer. According to multiple lung cancer cohorts, CHST11 is the only member of the carbohydrate sulfotransferase family associated with overall survival for lung adenocarcinomas, and it is highly related to smoking‐induced lung cancer patients. Based on the results of in vitro experiments, CHST11 expression contributes to tumor malignancy and promotes multiple fibrotic activators. Correlation‐based ingenuity pathway analysis indicated that CHST11‐related molecules contributed to pulmonary fibrosis or lung adenocarcinomas via similar upstream stimulators. Based on known molecular regulatory relationships, CHST11 has been associated with the regulation of TGF‐β and INFγ as important molecules contributing to fibrosis and cancer progression. Interestingly, WordCloud analysis revealed that CHST11‐related molecules are involved in regulation primarily by integrin signaling, and these relationships were consistently reflected in the analysis of cell lines and the clinical correlation. A CHST11 signature‐based drug repurposing analysis demonstrated that the CHST11/integrin axis could be targeted by AG‐1478 (Tyrphostin AG 1478), brefeldin A, geldanamycin and importazole. Conclusions This study provides the first demonstration that CHST11 may be used as a biomarker for pulmonary fibrosis or lung cancer, and the levels of CHST11 were increased by TGF‐β and INFγ. The molecular simulation analyses demonstrate that the CHST11/integrin axis is a potential therapeutic target for treating lung cancer.

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The potential of marine-derived piperazine alkaloids: Sources, structures and bioactivities

Zhang,

Sun,

et al. 2024

European Journal of Medicinal Chemistry

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Antitumor effect of the integrin α4 signaling inhibitor JK273 in non-small cell lung cancer NCI-H460 cells

Cited by 4 publications

References 13 publications

Integrins as therapeutic targets in the organ-specific metastasis of human malignant melanoma

Integrins as therapeutic targets in the organ-specific metastasis of human malignant melanoma

The CHST11 gene is linked to lung cancer and pulmonary fibrosis

The potential of marine-derived piperazine alkaloids: Sources, structures and bioactivities

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