RESUMEN
Sharing a common DNA binding motif called T-box, transcription factor T-box gene family controls embryonic development and is also involved in cancer progression and metastasis. Cancer metastasis shows therapy resistance and involves complex processes. Among them, epithelial-mesenchymal transition (EMT) triggers cancer cell invasiveness and the acquisition of stemness of cancer cells, called cancer stem cells (CSCs). CSCs are a small fraction of tumor bulk and are capable of self-renewal and tumorsphere formation. Recent progress has highlighted the critical roles of T-box genes in cancer progression, EMT, and CSC function, and such regulatory functions of T-box genes have emerged as potential therapeutic candidates for cancer. Herein we summarize the current understanding of the regulatory mechanisms of T-box genes in cancer, EMT, and CSCs, and discuss the implications of targeting T-box genes as anticancer therapeutics.
Asunto(s)
Transición Epitelial-Mesenquimal/genética , Proteínas de Neoplasias , Neoplasias , Células Madre Neoplásicas/metabolismo , Proteínas de Dominio T Box , Humanos , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/metabolismo , Neoplasias/genética , Neoplasias/metabolismo , Neoplasias/terapia , Proteínas de Dominio T Box/genética , Proteínas de Dominio T Box/metabolismoRESUMEN
Digital light processing bioprinting favors biofabrication of tissues with improved structural complexity. However, soft-tissue fabrication with this method remains a challenge to balance the physical performances of the bioinks for high-fidelity bioprinting and suitable microenvironments for the encapsulated cells to thrive. Here, we propose a molecular cleavage approach, where hyaluronic acid methacrylate (HAMA) is mixed with gelatin methacryloyl to achieve high-performance bioprinting, followed by selectively enzymatic digestion of HAMA, resulting in tissue-matching mechanical properties without losing the structural complexity and fidelity. Our method allows cellular morphological and functional improvements across multiple bioprinted tissue types featuring a wide range of mechanical stiffness, from the muscles to the brain, the softest organ of the human body. This platform endows us to biofabricate mechanically precisely tunable constructs to meet the biological function requirements of target tissues, potentially paving the way for broad applications in tissue and tissue model engineering.