LOXL2 (Lysyl Oxidase Like 2)

Our integrative epidemiological and experimental analyses identify LOXL2⁺ CAFs as a key stromal determinant of chemoresistance and poor prognosis in CRC. These findings highlight a clinically relevant stromal biomarker with potential for risk stratification and therapeutic targeting in colorectal cancer.

The functional interplay between LOXL2 and SYVN1 drives LIHC progression through the ECM-ERS-ERAD regulatory axis, and dual targeting of this axis may represent a potential therapeutic strategy.

We found that negativity for LOXL2 expression was an indicator of higher risk of death due to the disease. Our results suggest that lysyl oxidases such as LOXL2 are potential prognostic markers in mammary carcinomas of dogs.

Taken together, these findings suggest that FGF-23 promotes osteosarcoma cell migration and may contribute to metastasis through coordinated regulation of the miR-4463/LOXL2 axis via ERK, p38, and JNK signaling. Targeting FGF-23 or its downstream signaling cascades may offer a promising therapeutic approach for metastatic osteosarcoma.

The therapeutic process of PARP9 in PC may be achieved through the synergistic action of LOXL2 and PI3K/AKT signaling pathway. Our study reveals a potential link between PARP9 and PC, and targeting PARP9 and LOXL2 in monotherapy or combination therapy may provide novel strategies to advanced PC.

High LOXL2 expression is a reliable prognostic biomarker for various cancers, correlating with poor survival outcomes and advanced clinical features. LOXL2 may serve as a therapeutic target to improve cancer prognosis and treatment.

Besides, the combined ETV4, LOXL2 and NID1 as prognostic markers is more reliable than any one alone. Taken together, in this study, we demonstrated that ETV4 played a critical role in CRC metastasis, and unraveled the novel regulatory axis of ETV4/LOXL2/NID1, which contributed to the malignant progression of CRC.

In a murine model, dietary restriction alone, as well as treatment with each of the anticancer drugs used in this study (cisplatin, 5-fluorouracil, vincristine, irinotecan and cyclophosphamide), led to significant weight loss; however, dermal thinning was observed exclusively in the cisplatin and vincristine. Furthermore, the gene expression of Loxl1 and Loxl2-enzymes critical for collagen and elastin cross-linking was significantly diminished. These findings suggest that cisplatin and vincristine compromise dermal architecture by disrupting TGF-β signaling and extracellular matrix homeostasis, potentially contributing to premature skin aging in cancer survivors.

This study demonstrates that during early GBM progression, pericytes actively drive tumor angiogenesis through molecular reprogramming toward proliferative and pro-angiogenic phenotypes, with the integrated imaging-proteomics framework revealing potential therapeutic targets for disrupting pericyte-mediated vascular remodeling.

LOXL2 may affect the dynamic balance of the tumor microenvironment by regulating the immune function of macrophages and neutrophils in the extracellular matrix (ECM). The prediction model was established based on CCGA clinical data and COX regression analysis of LOXL2 gene expression data, which provides a theoretical foundation for the development of LOXL2-targeted therapy and the construction of genomic integrated prognostic model.

Ultimately, we elucidated the mechanism by which DHA induced cuproptosis in CRC cells, highlighting its inhibitory effect on LOXL2-mediated metabolic reprogramming of glycerophospholipids, thus suppressing tumor growth. DHA inhibits LOXL2, integral for glycerophospholipid metabolism in CRC, triggering cuproptosis and curbing tumor growth.

Combining BET inhibitors with PARPi abrogates LOXL2-mediated resistance, underscoring BRD4 dependency in this process. Our findings establish LOXL2 as a druggable epigenetic target to overcome PARPi resistance in HRP models of multiple tumor types, presenting a therapeutic strategy independent of HR status and holding significant clinical potential for expanding PARPi benefits to a broader patient population.