Exploring the role of Teneurin-4 in solid tumours: current evidence and potential therapeutic implications

Teneurin-4 (TENM4) has been reported as deregulated in a range of cancer histotypes; however, its functional contribution to tumour biology remains incompletely defined. Elevated TENM4 expression has been described in several malignancies, including breast, lung, colon, gastric, and pancreatic cancers, as well as in primary brain tumours, even if much of the available evidence remains correlative and predominantly based on in silico analyses. Emerging evidence, predominantly from triple negative breast cancer (TNBC) models, suggests a potential association between TENM4 expression and tumour cell plasticity, migratory behaviour, and stem-like properties, in part through focal adhesion kinase-associated signalling. Indeed, genetic silencing of TENM4 has been shown to reduce tumour spheroid formation and cell motility in murine and human in vitro TNBC models. In this review, we examine current knowledge of TENM4 expression patterns, structural characteristics, and reported molecular interactions in both physiological and pathological contexts. We review available interactome data, highlighting methodological constraints and variability between datasets, and discuss how proposed TENM4-associated networks may intersect with pathways regulating cytoskeletal dynamics, cell adhesion, and transcriptional programmes within the tumour microenvironment. We further outline key gaps in the field, including the need for more comprehensive in vivo validation and high-resolution interactomic approaches. The overview provided by this review highlights TENM4 as a relatively understudied molecule whose potential relevance in tumour cell plasticity and cancer progression requires further mechanistic and translational validation.