Mouse polyclonal to LOXL4, Host Mouse
- Known as:
- Mouse pab LOXL4, Host Mouse
- Catalog number:
- YF-PA26715
- Product Quantity:
- 50 uL
- Category:
- -
- Supplier:
- Abfron
- Gene target:
- Mouse polyclonal LOXL4 Host
Related genes to: Mouse polyclonal to LOXL4, Host Mouse
- Gene:
- LOXL4 NIH gene
- Name:
- lysyl oxidase like 4
- Previous symbol:
- -
- Synonyms:
- FLJ21889, LOXC
- Chromosome:
- 10q24.2
- Locus Type:
- gene with protein product
- Date approved:
- 2001-11-14
- Date modifiied:
- 2016-10-05
Related products to: Mouse polyclonal to LOXL4, Host Mouse
Related articles to: Mouse polyclonal to LOXL4, Host Mouse
- Lysyl oxidase-like protein 4 (LOXL4), a key member of the lysyl oxidase (LOX) family, is an important regulator of extracellular matrix (ECM) remodeling. Emerging evidence indicates that LOXL4 contributes to organ fibrosis by promoting collagen and elastin cross-linking, increasing matrix stiffness, and modulating aberrant mechanotransduction. In tumors, LOXL4 also facilitates the establishment of a fibrotic and immunosuppressive microenvironment. Through collagen cross-linking and ECM stiffening, LOXL4 can enhance TGF-β signaling, reinforce the ECM barrier, and promote immune exclusion, thereby altering the functions of immune cells such as T cells and macrophages and contributing to both fibrotic and tumor progression. Beyond its classical enzymatic activity, LOXL4 exerts non-enzymatic effects on cell adhesion, migration, and cell-microenvironment interactions, further expanding its pathological roles. In this review, we summarize the molecular characteristics, expression regulation, and enzymatic and non-enzymatic functions of LOXL4, with particular emphasis on the shared mechanisms linking fibrosis and tumor progression, including TGF-β signaling, ECM barrier formation, and immune microenvironment remodeling. We further discuss therapeutic strategies targeting LOXL4 and other LOX family members, as well as current challenges in clinical translation and opportunities for precision intervention. Collectively, LOXL4 represents a key molecular link between ECM remodeling, fibrotic responses, and tumor progression. However, the clinical development of LOXL4-targeted therapies remains limited by functional heterogeneity, the lack of robust biomarkers, and compensatory mechanisms within the LOX family. Future studies integrating precise patient stratification, dynamic assessment of therapeutic responses, and rational combination strategies may facilitate the clinical translation of LOXL4-targeted interventions. - Source: PubMed
Publication date: 2026/09/16
Tian YanLi Qingrong - Carotid atherosclerosis is a major etiologic substrate for ischemic stroke. Although imaging can characterize stenosis and plaque morphology, circulating biomarkers may better support screening and scalable risk stratification, yet reliable serum protein markers for carotid plaque, particularly for plaque instability, remain limited. - Source: PubMed
Guo ShuaiweiCui ShengyanZhang XiaoXing ZixuanSun YixinQin MingqianMa XiaoyingLi XiangyuMa YanGao PengChen YanfeiWang YabingYang BinChen JianChen FeiLu XiaJin JiaqiJiao LiqunWang Tao - Extracellular matrix (ECM) stiffness is known to impair T cell function, yet the underpinning molecular cascade remains undefined. This paper investigates the role of lysyl oxidase-like 4 (LOXL4) in ECM stiffening and CD8 T cell function in lung cancer. knockout and mouse recombinant LOXL4 protein systems, along with , , , and conditional knockout mouse models were established. ECM stiffness was measured by atomic force microscopy, and T cell exhaustion markers were analyzed using flow cytometry. RNA sequencing, ATAC-seq, CUT&Tag, chromatin immunoprecipitation-quantitative polymerase chain reaction, and luciferase assays were used to explore the underlying molecular mechanisms. Molecular docking was performed to explore Food and Drug Administration-approved agents targeting LOXL4. The results demonstrated that tumor-derived LOXL4 stiffened the ECM, which activates the mechanosensor Piezo1 in CD8 T cells, triggering Ca influx and downstream FAK1-YAP1 signaling. Nuclear YAP1 transactivated YBX1, which recruited the metabolic enzyme ACLY and the histone acetyltransferase KAT2A to exhaustion gene loci, epigenetically reinforcing terminal exhaustion. Conditional knockout of , , , and in murine CD8 T cells abolished stiffness-induced exhaustion and suppressed tumor growth. Acetyldigoxin was identified as a high-affinity LOXL4 inhibitor. It softened the ECM, disrupted the mechanosignaling-epigenetic axis, reversed CD8 T cell exhaustion, and synergized with anti-PD-1 blockade to achieve durable tumor regression. In conclusion, this study uncovers a mechanotransduction-to-epigenetic pathway where LOXL4-driven matrix stiffening induces CD8 T cell exhaustion. Repurposing acetyldigoxin as a LOXL4-targeted therapy offers a promising clinical strategy to overcome ECM-mediated immunotherapy resistance in lung cancer. - Source: PubMed
Publication date: 2026/09/11
Gu XuyuZhu YifeiXu LiXu XinnanJin KaiqiCho William CFang Qiyu - Triple-negative breast cancer (TNBC) is characterized by its aggressive phenotype and limited therapeutic options. FOXO1, a member of the O-class of forkhead transcription factors, has been implicated in various oncogenic processes, yet its specific role in TNBC remains to be fully elucidated. This study aimed to investigate the effects of the FOXO1-selective inhibitor, AS1842856, on the proliferation of the human TNBC cell line MDA-MB-231 and to identify the underlying molecular mechanisms. Treatment with AS1842856 significantly suppressed the proliferation of MDA-MB-231 cells in a dose-dependent manner. Additionally, AS1842856 suppressed the expression of lysyl oxidase-like 4 (LOXL4). Given LOXL4 is known to be involved in extracellular matrix remodeling and is frequently associated with cancer progression and metastasis, AS8142856 has been considered to suppress MDA-MB-231 cell migration. Interestingly, however, the knockdown of FOXO1 did not lead to a significant reduction in LOXL4 expression levels, suggesting that AS1842856 suppresses LOXL4 expression through FOXO1-independent mechanisms. We found that AS1842856-mediated ERK activation and intracellular reactive oxygen species are crucial in reducing LOXL4. Furthermore, the combined action of pharmacological inhibition of ERK pathways and AS1842856 suppressed MDA-MB-231 cell migration. These findings demonstrate that the ERK-LOXL4 signaling axis may play a critical role in the proliferation of TNBC cells. In conclusion, targeting the LOXL4 and ERK pathways pharmacologically could provide a novel therapeutic strategy for the treatment of aggressive breast cancers. - Source: PubMed
Publication date: 2026/06/05
Kamiya TetsuroKanaya AsumiOtsuka TomohiroHara Hirokazu - The recent inclusion of the Merlin clinicopathologic-gene expression profile (CP-GEP) assay in the National Comprehensive Cancer Network (NCCN) Melanoma Guidelines represents an important milestone in the clinical integration of molecular testing for cutaneous melanoma. Unlike earlier melanoma gene expression profile (GEP) assays, which focused primarily on prognostic risk stratification, CP-GEP was specifically developed to predict sentinel lymph node (SLN) metastasis risk by identifying early metastatic competence within primary melanomas, with additional prognostic utility. This review discusses the biological evidence supporting CP-GEP and examines how unbiased transcriptomic discovery converged with established insights from cancer cell biology, integrin signaling, focal adhesions, and extracellular matrix (ECM) remodeling to shape its conceptual framework. We further discuss how CP-GEP captures a transformation-associated biological state centered on an integrin- and TGF-β-dependent signaling axis (ITGB3, TGFBR1) that promotes pericellular proteolysis and ECM remodeling (PLAT, SERPINE2, LOXL4), inflammatory and angiogenic signaling (CXCL8, GDF15), and melanocytic lineage identity (MLANA). Collectively, these genes identify a dissemination-competent phenotype that is detectable within primary tumors before clinically apparent metastasis. Overall, the biological framework supporting CP-GEP reinforces the concept that altered adhesion signaling and ECM remodeling are central drivers of early melanoma metastasis and represent clinically actionable biomarkers for individualized melanoma management. - Source: PubMed
Publication date: 2026/08/03
Jing Frank ZMeves Alexander