Inhibition of
            <scp>DDR</scp>
            1‐
            <scp>BCR</scp>
            signalling by nilotinib as a new therapeutic strategy for metastatic colorectal cancer

Jeitany, Maya; Leroy, Cédric; Tosti, Priscillia; Lafitte, Marianne; Guet, Jordy Le; Simon, Valérie; Bonenfant, Débora; Robert, Bruno; Grillet, Fanny; Mollévi, Caroline; Messaoudi, Safia El; Otandault, Amaëlle; Canterel-Thouennon, Lucile; Busson, Muriel; Thierry, Alain R.; Martineau, Pierre; Pannequin, Julie; Roche, Serge; Sirvent, Audrey

doi:10.15252/emmm.201707918

Cited by 89 publications

(108 citation statements)

References 43 publications

(74 reference statements)

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“…These results imply that the OSCC cells might have been addicted to overexpressed DDR1 for their survival. In the same vein, targeting DDR1 alone or in combination with other chemotherapies have been suggested in several neoplasms, including metastatic colorectal cancer, K-RAS driven lung adenocarcinoma, and breast carcinoma [14,[52][53][54].…”

Section: Discussionmentioning

confidence: 99%

Discoidin Domain Receptor-1 (DDR1) is Involved in Angiolymphatic Invasion in Oral Cancer

Chen

Tsai

et al. 2020

Cancers

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The discoidin domain receptor-1 (DDR1) is a non-integrin collagen receptor recently implicated in the collective cell migration of other cancer types. Previously, we identified an elevated expression of DDR1 in oral squamous cell carcinoma (OSCC) cells. Through the data mining of a microarray dataset composed of matched tumor-normal tissues from forty OSCC patients, we distilled overexpressed genes statistically associated with angiolymphatic invasion, including DDR1, COL4A5, COL4A6 and PDPN. Dual immunohistochemical staining further confirmed the spatial locations of DDR1 and PDPN in OSCC tissues indicative of collective cancer cell invasion. An elevated DDR1 expression at both the transcription and protein level was observed by treating keratinocytes with collagen of fibrillar or basement membrane types. In addition, inhibition of DDR1 kinase activity in OSCC TW2.6 cells disrupted cell cohesiveness in a 2D culture, reduced spheroid invasion in a collagen gel matrix, and suppressed angiolymphatic invasion in xenograft tissues. Taken together, these results suggest that collagen deposition in the affected tissues followed by DDR1 overexpression could be central to OSCC tumor growth and angiolymphatic invasion. Thus, DDR1 inhibitors are potential therapeutic compounds in restraining oral cancer, which has not been previously explored.

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Section: Discussionmentioning

confidence: 99%

Discoidin Domain Receptor-1 (DDR1) is Involved in Angiolymphatic Invasion in Oral Cancer

Chen

Tsai

et al. 2020

Cancers

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“…In studies of Xie et al (), an association between DDR1 and invasion of gastric cancer cells via EMT has been shown in patients with gastric cancer. Jeitany et al () identified DDR1 as a therapeutic target in colorectal cancer and suggested that inhibition of DDR1 by tyrosine kinase inhibitors could be a useful medical approach in patients with metastatic colorectal cancer. Lu et al () reported that inhibition of DDR1 with a small chemical molecule inhibitor can suppress nasopharyngeal carcinoma cell in vitro.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of didscoidin domain receptor 1 reduces epithelial–mesenchymal transition and induce cell‐cycle arrest and apoptosis in prostate cancer cell lines

Azizi

Saberi

Fallahian

et al. 2019

Journal Cellular Physiology

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Didscoidin domain receptor 1 (DDR1) is involved in the progression of prostate cancer metastasis through stimulation of epithelial-mesenchymal transition (EMT). So DDR1 inhibition can be a helpful target for cancer metastasis prevention. So, we studied the effects of DDR1 inhibition on EMT as well as induction of cell-cycle arrest and apoptosis in prostate cancer cell lines. DDR1 expression was evaluated using reverse-transcription polymerase chain reaction and western blot analysis. The EMT-associated protein expression was determined using the western blot analysis and immunocytochemistry following treatment with various concentrations of DDR1 inhibitor. The activation of DDR1 and also downstream-signaling molecules Pyk2 and MKK7 were determined using western blot analysis. Cell survival and proliferation after DDR1 inhibition were evaluated using 3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyltetrazolium bromide, bromodeoxyuridine, and colony formation assays. Flow cytometry analysis was used to determine the effects of DDR1 inhibition on cellcycle arrest and apoptosis using annexin V/propidium iodide-based flow cytometry. Results showed that the protein expression of N-cadherin and vimentin were decreased whereas protein expression of E-cadherin was increased after DDR1 inhibition. Results of our western blot analysis indicated that DDR1 inhibitor effectively downregulated P-DDR1, P-Pyk2, and P-MKK7 levels. This result also showed that DDR1 inhibition decreased cell survival and proliferation, induced G1 cell-cycle arrest, induced apoptosis by an increase in the Bax/Bcl-2 ratio and depletion of the mitochondrial membrane potential, and also by reactive oxygen species creation in prostate cancer cells. These data show that DDR1 inhibition can result in the EMT prevention via inhibition of Pyk2 and MKK7 signaling pathway and induces cell-cycle arrest and apoptosis in prostate cancer cell lines. Thus, this study identifies DDR1 as an important target for modulating EMT and induction of apoptosis in prostate cancer cells. K E Y W O R D S apoptosis, cell-cycle arrest, discoidin domain receptor 1 (DDR1), EMT

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“…These inhibitors are approved by the FDA and could constitute a new treatment for patients overexpressing DDRs in cancers. For example, recently it has been shown that nilotinib inhibits DDR1 kinase activation and reduces invasion in metastatic colorectal cancer [127]. Dasatinib efficiency has been proven several times.…”

Section: Inhibition Of the Ddrsmentioning

confidence: 99%

Multitasking discoidin domain receptors are involved in several and specific hallmarks of cancer

Henriet

Sala

Hammoud

et al. 2018

Cell Adhesion & Migration

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Discoidin domain receptors, DDR1 and DDR2, are two members of collagen receptor family that belong to tyrosine kinase receptor subgroup. Unlike other matrix receptor-like integrins, these collagen receptors have not been extensively studied. However, more and more studies are focusing on their involvement in cancer. These two receptors are present in several subcellular localizations such as intercellular junction or along type I collagen fibers. Consequently, they are involved in multiple cellular functions, for instance, cell cohesion, proliferation, adhesion, migration and invasion. Furthermore, various signaling pathways are associated with these multiple functions. In this review, we highlight and characterize hallmarks of cancer in which DDRs play crucial roles. We discuss recent data from studies that demonstrate the involvement of DDRs in tumor proliferation, cancer mutations, drug resistance, inflammation, neo-angiogenesis and metastasis. DDRs could be potential targets in cancer and we conclude this review by discussing the different ways to inhibits them.

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Inhibition of DDR 1‐ BCR signalling by nilotinib as a new therapeutic strategy for metastatic colorectal cancer

Cited by 89 publications

References 43 publications

Discoidin Domain Receptor-1 (DDR1) is Involved in Angiolymphatic Invasion in Oral Cancer

Discoidin Domain Receptor-1 (DDR1) is Involved in Angiolymphatic Invasion in Oral Cancer

Inhibition of didscoidin domain receptor 1 reduces epithelial–mesenchymal transition and induce cell‐cycle arrest and apoptosis in prostate cancer cell lines

Multitasking discoidin domain receptors are involved in several and specific hallmarks of cancer

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