Cancer‑associated fibroblast‑derived LRRC15 promotes the migration and invasion of triple‑negative breast cancer cells via Wnt/β‑catenin signalling pathway regulation

Yang, Yang; Wu, Haiying; Fan, Shaoxia; Bi, Yanqing; Hao, Min; Shang, Jian

doi:10.3892/mmr.2021.12518

Cited by 11 publications

(11 citation statements)

References 36 publications

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“…Previous studies have also demonstrated that LRRC15 may play a vital role in reducing bone resorption and promoting bone formation by acting as a suppressor of NF- κ B [ 56 ]. Furthermore, LRRC15 was found to be overexpressed in aggressive cancer cells, such as breast cancer [ 57 ], ovarian cancer [ 58 ], and osteosarcoma [ 59 ].…”

Section: Discussionmentioning

confidence: 99%

Identification and Validation of Hub Genes for Predicting Treatment Targets and Immune Landscape in Rheumatoid Arthritis

et al. 2022

BioMed Research International

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Background. Rheumatoid arthritis (RA) is recognized as a chronic inflammatory disease featured by pathological synovial inflammation. Currently, the underlying pathophysiological mechanisms of RA remain unclear. In the study, we attempted to explore the underlying mechanisms of RA and provide potential targets for the therapy of RA via bioinformatics analysis. Methods. We downloaded four microarray datasets (GSE77298, GSE55235, GSE12021, and GSE55457) from the GEO database. Firstly, GSE77298 and GSE55457 were identified DEGs by the “limma” and “sva” packages of R software. Then, we performed GO, KEGG, and GSEA enrichment analyses to further analyze the function of DEGs. Hub genes were screened using LASSO analysis and SVM-RFE analysis. To further explore the differences of the expression of hub genes in healthy control and RA patient synovial tissues, we calculated the ROC curves and AUC. The expression levels of hub genes were verified in synovial tissues of normal and RA rats by qRT-PCR and western blot. Furthermore, the CIBERSORTx was implemented to assess the differences of infiltration in 22 immune cells between normal and RA synovial tissues. We explored the association between hub genes and infiltrating immune cells. Results. CRTAM, CXCL13, and LRRC15 were identified as RA’s potential hub genes by machine learning and LASSO algorithms. In addition, we verified the expression levels of three hub genes in the synovial tissue of normal and RA rats by PCR and western blot. Moreover, immune cell infiltration analysis showed that plasma cells, T follicular helper cells, M0 macrophages, M1 macrophages, and gamma delta T cells may be engaged in the development and progression of RA. Conclusions. In brief, our study identified and validated that three hub genes CRTAM, CXCL13, and LRRC15 might involve in the pathological development of RA, which could provide novel perspectives for the diagnosis and treatment with RA.

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Section: Discussionmentioning

confidence: 99%

Identification and Validation of Hub Genes for Predicting Treatment Targets and Immune Landscape in Rheumatoid Arthritis

et al. 2022

BioMed Research International

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“…In their study, they found that LRRC15 expressing CAFs promoted matrix metalloproteinase (MMP) expression in TNBC cell lines, which further mediated migration and invasion (57). However, the impact of LRRC15 on MMP expression may be context dependent as LRRC15 expression in astrocytes was not associated with MMP overexpression (50).…”

Section: Role In Cancermentioning

confidence: 99%

“…2B) and suggests that it can be implicated as a potential antitumor target, a concept further supported by the development of ABBV-085, an LRRC15-antibody targeted drug conjugate (17,21). In addition to its potential role in integrin signaling, LRRC15 has recently been shown to promote TNBC tumor migration and invasion by regulating the Wnt/b-catenin signaling pathway (57).…”

Section: Role In Cancermentioning

confidence: 99%

“…In a study by Yang and colleagues, high LRRC15 expression in CAFs of TNBC cell lines was associated with increased cytoplasmic and nuclear b-catenin, which drove cancer cell migration and invasion (57). Mechanistically, LRRC15 expression was demonstrated to decrease the expression of Axin1, a protein member of the destruction complex that promotes the degradation of b-catenin, leading to increased b-catenin levels (57).…”

Section: Role In Cancermentioning

confidence: 99%

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Exploiting LRRC15 as a Novel Therapeutic Target in Cancer

et al. 2022

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Abundant fibrotic stroma is a typical feature of most solid tumors, and stromal activation promotes oncogenesis, therapy resistance, and metastatic dissemination of cancer cells. Therefore, targeting the tumor stroma in combination with standard-of-care therapies has become a promising therapeutic strategy in recent years. The leucine-rich repeat-containing protein (LRRC15) is involved in cell-cell and cell-matrix interactions and came into focus as a promising anti-cancer target owing to its overexpression in mesenchymal-derived tumors such as sarcoma, glioblastoma, and melanoma and in cancer-associated fibroblasts in the microenvironment of breast, head and neck, lung, and pancreatic tumors. Effective targeting of LRRC15 using specific antibody-drug conjugates (ADC) has the potential to improve the outcome of patients with LRRC15-positive cancers of mesenchymal origin or stromal desmoplasia. Moreover, LRRC15 expression may serve as a predictive biomarker that could be utilized in the preclinical assessment of cancer patients to support personalized clinical outcomes. This review focuses on the role of LRRC15 in cancer, including clinical trials involving LRRC15-targeted therapies, such as the ABBV-085 ADC for patients with LRRC15-positive tumors. This review spans perceived knowledge gaps and highlights the clinical avenues that need to be explored to provide better therapeutic outcomes in patients.

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“…According to their findings, CAFs enhance TNBC cell migration, invasion, and proliferation and participate in the EMT process via the Wnt/β-catenin pathway [ 151 ]. Other studies found that CAFs with high expression of leucine-rich repeat-containing protein 15 (LRRC15) increased cell migration and invasion by influencing the Wnt/β-catenin signaling pathway using MDA-MB-231 and MDA-MB-468 TNBC cell lines [ 152 ].…”

Section: Thymoquinone (Tq) Targeting the Cellular Components Of Tmementioning

confidence: 99%

Therapeutic Potential of Thymoquinone in Triple-Negative Breast Cancer Prevention and Progression through the Modulation of the Tumor Microenvironment

et al. 2021

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To date, the tumor microenvironment (TME) has gained considerable attention in various areas of cancer research due to its role in driving a loss of immune surveillance and enabling rapid advanced tumor development and progression. The TME plays an integral role in driving advanced aggressive breast cancers, including triple-negative breast cancer (TNBC), a pivotal mediator for tumor cells to communicate with the surrounding cells via lymphatic and circulatory systems. Furthermore, the TME plays a significant role in all steps and stages of carcinogenesis by promoting and stimulating uncontrolled cell proliferation and protecting tumor cells from the immune system. Various cellular components of the TME work together to drive cancer processes, some of which include tumor-associated adipocytes, fibroblasts, macrophages, and neutrophils which sustain perpetual amplification and release of pro-inflammatory molecules such as cytokines. Thymoquinone (TQ), a natural chemical component from black cumin seed, is widely used traditionally and now in clinical trials for the treatment/prevention of multiple types of cancer, showing a potential to mitigate components of TME at various stages by various pathways. In this review, we focus on the role of TME in TNBC cancer progression and the effect of TQ on the TME, emphasizing their anticipated role in the prevention and treatment of TNBC. It was concluded from this review that the multiple components of the TME serve as a critical part of TNBC tumor promotion and stimulation of uncontrolled cell proliferation. Meanwhile, TQ could be a crucial compound in the prevention and progression of TNBC therapy through the modulation of the TME.

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Cancer‑associated fibroblast‑derived LRRC15 promotes the migration and invasion of triple‑negative breast cancer cells via Wnt/β‑catenin signalling pathway regulation

Cited by 11 publications

References 36 publications

Identification and Validation of Hub Genes for Predicting Treatment Targets and Immune Landscape in Rheumatoid Arthritis

Identification and Validation of Hub Genes for Predicting Treatment Targets and Immune Landscape in Rheumatoid Arthritis

Exploiting LRRC15 as a Novel Therapeutic Target in Cancer

Therapeutic Potential of Thymoquinone in Triple-Negative Breast Cancer Prevention and Progression through the Modulation of the Tumor Microenvironment

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