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Published on: July 20, 2019
Exploring the role of Teneurin-4 in solid tumours: current evidence and potential therapeutic implications
Davide Loggia1, Giulia Peppino1, Chiara Vit1
1Department of Molecular Biotechnology and Health Sciences, University of Turin, Turin, 10126, Italy.
Abstract:
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.
Insights
Teneurin-4 (TENM4) is linked to cancer progression and cell plasticity. Further research is needed to validate its role in tumour biology and potential as a therapeutic target.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Teneurin-4 (TENM4) expression is deregulated across various cancer types, but its functional role in tumor biology is not fully understood.
- Existing evidence, primarily correlative and in silico, suggests TENM4 upregulation in breast, lung, colon, gastric, pancreatic cancers, and brain tumors.
Purpose of the Study:
- To review current knowledge on TENM4 expression, structure, and molecular interactions in physiological and pathological settings.
- To discuss TENM4's potential role in tumor cell plasticity, migration, and stem-like properties, particularly in triple-negative breast cancer (TNBC).
- To identify knowledge gaps and the need for further validation of TENM4's function in cancer.
Main Methods:
- Literature review of existing studies on TENM4 expression patterns.
- Analysis of available interactome data and proposed TENM4-associated signaling networks.
- Examination of evidence from triple-negative breast cancer models regarding TENM4's functional impact.
Main Results:
- TENM4 expression is elevated in multiple cancer types, with emerging evidence linking it to tumor cell plasticity and motility, potentially via focal adhesion kinase signaling.
- Genetic silencing of TENM4 reduced spheroid formation and motility in vitro TNBC models.
- Proposed TENM4 networks may influence cytoskeletal dynamics, cell adhesion, and transcriptional programs within the tumor microenvironment.
Conclusions:
- TENM4 is an understudied molecule with potential implications in cancer cell plasticity and progression.
- Further mechanistic studies and in vivo validation are crucial to confirm TENM4's role and therapeutic potential.
- High-resolution interactomic approaches are needed to fully elucidate TENM4's molecular interactions and functions.
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