2021
DOI: 10.1002/1878-0261.13138
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A small molecule targeting CHI3L1 inhibits lung metastasis by blocking IL‐13Rα2‐mediated JNK‐AP‐1 signals

Abstract: Our previous big data analyses showed a high level of association between chitinase 3 like1 (CHI3L1) expression and lung tumor development. In the present study, we investigated whether a CHI3L1‐inhibiting chemical, 2‐({3‐[2‐(1‐cyclohexen‐1‐yl)ethyl]‐6,7‐dimethoxy‐4‐oxo‐3,4‐dihydro‐2‐quinazolinyl}sulfanyl)‐N‐(4‐ethylphenyl)butanamide (K284), could inhibit lung metastasis and studied its mechanism of action. We investigated the antitumor effect of K284 both in vitro and in vivo. K284 (0.5 mg·kg−1 body weight) s… Show more

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Cited by 19 publications
(9 citation statements)
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“…8e ). Individual invasion program genes are coherently expressed in macrophages, only increase in non-responders, and include known invasion and metastasis mediators ( CTSL 5 9 , CTSD 60 , CTSB 61 , CHI3L1 62 , SPP1 63 , PLIN2 64 ). Moreover, the invasion program includes cholesterol metabolism genes ( APOE 65,66 , APOC1 67 , CYP27A1 68 , GPNMB 69 ), some which have been linked to the suppression of inflammatory cytokine release (IL-6, TNF-alpha).…”
Section: Resultsmentioning
confidence: 99%
“…8e ). Individual invasion program genes are coherently expressed in macrophages, only increase in non-responders, and include known invasion and metastasis mediators ( CTSL 5 9 , CTSD 60 , CTSB 61 , CHI3L1 62 , SPP1 63 , PLIN2 64 ). Moreover, the invasion program includes cholesterol metabolism genes ( APOE 65,66 , APOC1 67 , CYP27A1 68 , GPNMB 69 ), some which have been linked to the suppression of inflammatory cytokine release (IL-6, TNF-alpha).…”
Section: Resultsmentioning
confidence: 99%
“…Further progress in research on the direct interactions of CHI3L1 expression with the expression and activity of PD-L1 due to the detailed study of PD-L1 in the tumor pathology and the use of the knowledge about PD-L1 not only in immunotherapy but also in dynamic phototherapy may contribute to overcoming resistance to immunotherapies, chemotherapy, and radiotherapy [ 71 , 72 ]. Due to ongoing studies using molecules targeting CHI3L1 expression such as small molecules targeting YKL-40 and chitosan, our high-dimensional analysis demonstrating associations between CHI3L1 expression and processes related to immunosuppression and the tumor microenvironment in colorectal cancer may contribute to a more thorough understanding and shape further research on the role of CHI3L1 in the pathology of colorectal cancer [ 73 , 74 ].…”
Section: Discussionmentioning
confidence: 99%
“…It is unknown which YKL-40-receptor binding is the one(s) leading to cancer-promoting effects observed in this and other pre-clinical studies. Recently, the chitin-binding domain was associated with the binding domain to IL13Rα2, suggesting that COS could block the interaction between YKL-40 and IL13Rα2 [ 45 ]. This could be one of the ways that COS exert their effects on tumor growth.…”
Section: Discussionmentioning
confidence: 99%