Mmp14, also known as membrane-type matrix metalloproteinase, is a key regulator in cell-cell and cell-extracellular matrix (ECM) communication. It influences multiple extracellular and plasma membrane proteins, mediating processes like ECM degradation, remodeling, cell invasion, and cancer metastasis. It is involved in functional networks related to protein digestion, absorption, extracellular matrix receptor interaction, and focal adhesion [1,3].

Mmp14 is highly expressed in most sarcomas, regulating tumor microenvironment communication in connective tissues [1]. In lipoedema, it may be part of a dysfunctional axis with caveolin 1 and oestrogen receptors [2]. High Mmp14 expression in gastric, colorectal, and oral squamous cell carcinomas is associated with worse prognosis, deeper invasion, and metastasis [3,4,6]. In glioblastoma, its expression is linked to radioresistance, and inhibition of Mmp14 can enhance the radiosensitization induced by histone deacetylase inhibitors [5]. In esophageal cancer, MMP14-positive tumor-associated fibroblasts can inhibit PD-1 immunotherapy through exosomal tsRNA-10522 [7]. In corneal neovascularization, Mmp14-containing exosomes can cleave VEGFR1 and promote endothelial cell migration and proliferation [8].

In conclusion, Mmp14 is crucial in regulating cell-matrix interactions and various disease-related processes such as cancer metastasis, lipoedema development, and glioblastoma radioresistance. Studies on Mmp14, especially through loss-of-function models in relevant diseases, help us understand its role in these pathological conditions and may provide potential therapeutic targets for treatment [1-10].