TBX6 promotes proliferation, invasion, and migration in colorectal cancer: Integrated transcriptomic and protein interaction network analysis.

Authors

Nianjie Zhang, Lei Wan, Nian He, Xu Chen, Xuefeng Yang, Jing Wang

Published in

Gene. Pages 150305. Jul 04, 2026. Epub Jul 04, 2026.

Abstract

The role of T-box transcription factor 6 (TBX6), a developmental transcription factor, in tumor initiation and progression in colorectal cancer (CRC) remains unclear. The present study investigated the expression pattern, biological functions, and downstream transcriptional regulatory networks of TBX6 in CRC. Public databases, clinical cohorts, functional assays, xenograft models, and RNA sequencing coupled with Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, and protein-protein interaction analyses were used to define TBX6-associated molecular alterations. TBX6 was markedly upregulated in CRC tissues and cell lines, and its high expression was associated with advanced stage, lymph node metastasis, and poor survival. Functionally, TBX6 promoted proliferation, migration, invasion, and epithelial-mesenchymal transition in CRC cells in vitro, whereas TBX6 knockdown suppressed these malignant phenotypes and inhibited tumor growth with reduced proliferation and increased apoptosis in vivo. Transcriptomic analyses showed that TBX6 knockdown induced coordinated gene expression reprogramming and altered multiple tumor-related pathways. Protein-protein interaction analysis identified C-X-C motif chemokine ligand 14 (CXCL14), NOTUM, adrenoceptor α2A (ADRA2A), and melanin-concentrating hormone receptor 1 (MCHR1) as hub nodes within the TBX6-regulated network. Mechanistically, TBX6 knockdown regulated CXCL14 expression and attenuated Wnt/β-catenin signaling, findings that were further validated in xenograft tissues. These results indicate that TBX6 is aberrantly reactivated in CRC and promotes tumor progression through transcriptional network remodeling, suggesting that TBX6 may represent a potential prognostic biomarker and therapeutic target.

PMID:
42401341
Bibliographic data and abstract were imported from PubMed on 05 Jul 2026.

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