MMP14 (Matrix Metallopeptidase 14)

This FLEX-based single-cell atlas revealed critical transcriptional programs and cell-cell interactions, identifying SEMA4D and LMCD1 as promising therapeutic targets for liver fibrosis.

It is a major promoter of cell invasion and tissue destruction in diseases, such as cancer and arthritis, and is a crucial enzyme that maintains fibrillar collagen homeostasis in stromal tissue. This review discusses the current understanding of the function and regulation of this important cell surface proteinase in health and disease.

These data support the PG-CAR-T cells for clinical trial of liver cancer.

Concurrently, Theranekron® induced transcriptional changes associated with mitochondrial and SMAD-dependent apoptotic pathways. Theranekron® acts as a cell-context-specific modulator, simultaneously regulating PI3K/AKT/PDK1, NF-κB and SMAD pathways to restore ECM integrity and modulate apoptotic signaling pathways in Caco-2 CRC cells, suggesting its potential as a multi-target experimental therapeutic candidate in in vitro CRC models.

To explore therapeutic implications, transcriptomics-guided drug repositioning combined with molecular docking analysis identified five candidate compounds-celastrol, fedratinib, pevonedistat, tozasertib, and withaferin A-predicted to target key network hubs. Overall, this in silico study provides a ceRNA-centered regulatory framework for GC and prioritizes biologically informed biomarkers and repositioned drug candidates with potential applicability across other malignancies to converge precision oncology.

Additionally, dysregulation of CDK activity through CCND2, CCND3, and CCNB2 overexpression indicated accelerated cell cycle progression and evasion of DNA damage checkpoints. Together, this integrative analysis highlights ECM remodeling, cytoskeletal dynamics, and lipid metabolism as major contributors to cisplatin resistance and identifies potential therapeutic markers for TNBC.

However, the development of MMP14 inhibitors for clinical use has been unsuccessful, partly due to the unclear mechanism of the interaction between TIMP2 and MMP14. In this work, we successfully obtained the N-terminal domain of TIMP2 (N-TIMP2) protein through a four-segment-three-ligation total chemical synthesis strategy and confirmed its correct refolding, thus providing a novel tool for elucidating the specific interaction mechanisms between N-TIMP2 and MMP14.

Among the top pathways identified based on FDR and P value were receptor binding signaling, regulation of cell migration, the extracellular matrix, and the AGE-RAGE signaling pathway. The results predict that the hub genes correlated with angiogenesis may serve as potential therapeutic targets or could be biomarkers for breast cancer.

Transcriptomic correlation analyses demonstrated that differentially expressed MMPs interact with genes likely involved in cell adhesion, ECM organization, and immune response, such as COL1A2, CDH11, KIRREL1, PPP1R14D, CEACAM8, ZNF423, and PRRX1. The enrichment of biological pathways suggests involvement in processes such as ECM organization, collagen and proteoglycan degradation, suggesting that these genes possibly are involved in carcinogenic dynamics, supporting the role of MMPs in tumor ECM reorganization.

TIMPs display contrasting expression profiles and distinct pathway associations in breast cancer. TIMP1 emerges as the only consistently overexpressed inhibitor, while TIMP4 appears as a promising prognostic marker with unique MMP correlations that may influence tumor behaviors.

This review systematically integrates current knowledge on BAI1, focusing on its genomic regulatory mechanisms, structural isoform diversity, and multidimensional biological functions. It also underscores the need to explore the translational potential of BAI1 in oncology, neurodegenerative diseases, and immune dysregulation, which is essential for advancing our understanding of this complex receptor and its therapeutic applications.