Co-expression of DDR2 and IFITM1 promotes breast cancer cell proliferation, migration and invasion and inhibits apoptosis

Wu, Chenlu; Ying, Jiafei; Dai, Mingzhi; Peng, Jing; Zhang, Danhua

doi:10.1007/s00432-022-04110-1

Cited by 11 publications

(12 citation statements)

References 41 publications

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“…Although the roles of DDR2 in the regulation of cell homeostasis, migration or cell cycle remain controversial, a growing number of reports have implicated DDR2 as a key driver of cell proliferation in fibroblasts [ 50 , 51 ], chondrocytes [ 50 , 52 , 53 ], hepatic stellate cells [ 54 ], lung squamous cancer cell lines [ 55 ], osteoblasts [ 53 ], and breast cancer cell lines [ 56 ]. This is consistent with our findings that DDR2 is also required for proper neuroblastoma cell proliferation.…”

Section: Discussionmentioning

confidence: 99%

DDR2 signaling and mechanosensing orchestrate neuroblastoma cell fate through different transcriptome mechanisms

Vessella,

Xiang,

Xiao

et al. 2024

FEBS Open Bio

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The extracellular matrix (ECM) regulates carcinogenesis by interacting with cancer cells via cell surface receptors. Discoidin Domain Receptor 2 (DDR2) is a collagen‐activated receptor implicated in cell survival, growth, and differentiation. Dysregulated DDR2 expression has been identified in various cancer types, making it as a promising therapeutic target. Additionally, cancer cells exhibit mechanosensing abilities, detecting changes in ECM stiffness, which is particularly important for carcinogenesis given the observed ECM stiffening in numerous cancer types. Despite these, whether collagen‐activated DDR2 signaling and ECM stiffness‐induced mechanosensing exert similar effects on cancer cell behavior and whether they operate through analogous mechanisms remain elusive. To address these questions, we performed bulk RNA sequencing (RNA‐seq) on human SH‐SY5Y neuroblastoma cells cultured on collagen‐coated substrates. Our results show that DDR2 downregulation induces significant changes in the cell transcriptome, with changes in expression of 15% of the genome, specifically affecting the genes associated with cell division and differentiation. We validated the RNA‐seq results by showing that DDR2 knockdown redirects the cell fate from proliferation to senescence. Like DDR2 knockdown, increasing substrate stiffness diminishes cell proliferation. Surprisingly, RNA‐seq indicates that substrate stiffness has no detectable effect on the transcriptome. Furthermore, DDR2 knockdown influences cellular responses to substrate stiffness changes, highlighting a crosstalk between these two ECM‐induced signaling pathways. Based on our results, we propose that the ECM could activate DDR2 signaling and mechanosensing in cancer cells to orchestrate their cell fate through distinct mechanisms, with or without involving gene expression, thus providing novel mechanistic insights into cancer progression.

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Section: Discussionmentioning

confidence: 99%

DDR2 signaling and mechanosensing orchestrate neuroblastoma cell fate through different transcriptome mechanisms

Vessella,

Xiang,

Xiao

et al. 2024

FEBS Open Bio

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“…And plays a key role in the antiproliferative action of IFN-gamma either by inhibiting the ERK activation or by arresting cell growth in the G1 phase in a p53-dependent manner. It has been shown that IFITM1 is tightly regulated by the proliferation, migration, and invasion of breast cancer and inhibits apoptosis, and that inhibition of IFITM1 expression by disrupting interferon-α and NF-κB crosstalk can attenuate triple-negative breast cancer progression (Wu et al, 2022, Zhao et al, 2021, which may be one of the novel immunomarkers for endometrial cancer stromal cells (Zhao et al, 2021), and knockdown of IFITM1 in pancreatic cancer was also found to inhibit the proliferation of cells, that induced cell cycle arrest and apoptosis, and inhibited cancer progression (Zhang et al, 2020). In small-cell lung cancer, IFITM1 overexpression was found to promote distant metastasis, and in lung adenocarcinoma, IFITM1 expression was found to be signi cantly associated with increased microvessel density and correlated with patient prognosis (Koh et al, 2019).…”

Section: Discussionmentioning

confidence: 99%

Risk prediction for Dermatomyositis-associated hepatocellular carcinoma

Zhang

Liu

et al. 2023

Preprint

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Objective To explore dermatomyositis signature genes as potential biomarkers of hepatocellular carcinoma and their associated molecular regulatory mechanisms. Methods Based on the mRNA-Seq data of dermatomyositis and hepatocellular carcinoma in public databases, five dermatomyositis signature genes were screened by LASSO regression analysis and support vector machine (SVM) algorithm, and their biological functions in dermatomyositis with hepatocellular carcinoma were investigated, and a nomogram risk prediction model for hepatocellular carcinoma was constructed and its predictive efficiency was initially evaluated. The immune profile in hepatocellular carcinoma was examined based on the CIBERSORT and ssGSEA algorithms, and the correlation between five dermatomyositis signature genes and tumor immune cell infiltration and immune checkpoints in hepatocellular carcinoma was investigated. Results The expression levels of five dermatomyositis signature genes were significantly altered in hepatocellular carcinoma and showed good diagnostic efficacy for hepatocellular carcinoma, suggesting that they may be potential predictive targets for hepatocellular carcinoma, and the risk prediction model based on five dermatomyositis signature genes showed good risk prediction efficacy for hepatocellular carcinoma and has good potential for clinical application. In addition, we also found that the upregulation of SPP1 expression may activate the PI3K/ART signaling pathway through integrin-mediated activation, which in turn regulates the development and progression of hepatocellular carcinoma. Conclusion LY6E, IFITM1, GADD45A, MT1M, and SPP1 are potential predictive targets for new-onset hepatocellular carcinoma in patients with dermatomyositis, and the upregulation of SPP1 expression may activate the PI3K/ART signaling pathway through the mediation of integrins to promote the development and progression of hepatocellular carcinoma.

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“…Although the roles of DDR2 in the regulation of cell homeostasis, migration or cell cycle remain controversial, a growing number of reports have implicated DDR2 as a key driver of cell proliferation in fibroblasts (41, 42), chondrocytes (41, 43, 44), hepatic stellate cells (45), lung squamous cancer cell lines (46), osteoblasts (44), and breast cancer cell lines (47). Therefore, it is not surprising to observe that DDR2 is also required for proper neuroblastoma cell proliferation.…”

Section: Discussionmentioning

confidence: 99%

The roles of DDR2 and substrate stiffness on cancer cell transcriptome and proliferation

Vessella,

Xiang,

Xiao

et al. 2023

Preprint

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The interactions between cancer cells and the ECM regulate carcinogenesis. The collagen receptor kinase DDR2 is dysregulated in certain cancer cells, but its precise role in these malignancies remains unclear. In this study, we perform RNA-seq to determine how DDR2 and the biomechanical environment regulate cancer cell behaviors. We show that DDR2 knockdown in SH-SY5Y neuroblastoma cells inhibits proliferation and promotes senescence by regulating relevant genes. Increasing substrate stiffness reduces proliferation and promotes cell spreading but does not change senescence or transcriptome. Furthermore, DDR2 knockdown modulates cellular responses to substrate stiffness changes, unraveling a crosstalk between DDR2 and mechanosensing. These findings indicate DDR2 and ECM biomechanics regulate cancer cell behavior through distinct mechanisms, providing new mechanistic insights of cancer progression.

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Co-expression of DDR2 and IFITM1 promotes breast cancer cell proliferation, migration and invasion and inhibits apoptosis

Cited by 11 publications

References 41 publications

DDR2 signaling and mechanosensing orchestrate neuroblastoma cell fate through different transcriptome mechanisms

DDR2 signaling and mechanosensing orchestrate neuroblastoma cell fate through different transcriptome mechanisms

Risk prediction for Dermatomyositis-associated hepatocellular carcinoma

The roles of DDR2 and substrate stiffness on cancer cell transcriptome and proliferation

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