A cutting-edge investigation of the multifaceted role of SOX family genes in cancer pathogenesis through the modulation of various signaling pathways

Functional & Integrative Genomics, Journal Year: 2025, Volume and Issue: 25(1)

Published: Jan. 4, 2025

Language: Английский

Identification of gene signatures and transcription factors associated with colorectal cancer through computational based approach

Human Gene, Journal Year: 2025, Volume and Issue: unknown, P. 201405 - 201405

Published: April 1, 2025

Language: Английский

SOX17 orchestrates immune evasion in early colorectal adenomas and cancers

Immunology, Journal Year: 2024, Volume and Issue: 173(2), P. 422 - 424

Published: July 23, 2024

The complex crosstalk between cancer and the immune system is a pivotal aspect of tumour progression metastasis. ability cells to evade clearance hallmark cancer, understanding mechanisms underlying this process crucial for development effective immunotherapies. A recent study in Nature may explain how colorectal adenomas host surveillance early stages [1]. researchers reveal SRY-box containing gene 17(SOX17) assists tumours evading recognition attack early-stage cancers, providing new insights into tumorigenesis offering potential targets therapeutic intervention. Colorectal (CRC) third most common second leading cause cancer-related deaths worldwide [2]. Despite significant advancements chemotherapy targeted therapies, prognosis locally advanced or metastatic CRC patients remains poor [3]. With advent immunotherapy, it has revolutionised treatment become mainstay microsatellite instability-high (MSI-H)/deficient mismatch repair (dMMR) [4, 5]. However, cancers (approximately 85%) 95%) are characterised by stable (MSS)/proficient (pMMR) status, which highly immune-suppressive microenvironment that often leads resistance against immunotherapy [6, 7]. Thus, remarkably changed landscape introduced opportunities challenges treating CRC. SOX17, well-known member SOX transcription factor family, associated with diagnosis, staging, various [8, 9]. In study, Goto et al. used combination vitro organoid cultures vivo transplantation assays examine adaptability naive colon organoids AKP mutations (Apc-null, KrasG12D Trp53-null) an immunocompetent mouse model. Through comprehensive transcriptomic (RNA-seq) chromatin accessibility (ATAC-seq) analyses, they identified SOX17 as key regulator significantly upregulated vivo. To elucidate functional impact utilised CRISPR–Cas9 genome editing ablate expression organoids, loss notably impaired growth mice resulted substantial increase cell infiltration, particularly CD4+T CD8+ T cells. Single-cell RNA sequencing (scRNA-seq) was performed on sorted CD45+ from control SOX17-null at time points post-transplantation, detailed picture dynamics profiles. Notably, markedly reduces persist mice, suggesting critical role evasion. Mechanistically, suppresses respond interferon-γ (IFNγ), cytokine anti-tumour responses, directly repressing IFNγ receptor components. Moreover, mediates foetal reprogramming cells, decrease major histocompatibility class I (MHC-I) immune-silent phenotype. Additionally, drives differentiation away stem-like LGR5+ typically more immunogenic, towards LGR5− lower MHC-I, further facilitating This suggests not only affects immediate response but also influences long-term plasticity potentially contributing emergence aggressive therapy-resistant phenotypes. An alternative explanation evasion observed progresses stage invasive state could be involvement another plays suppressing antitumor immunity within CRC, namely, signal transducer activator 3 (STAT3) [10]. Understanding ultimately inactivated identifying specific molecular pathways interactions subsequently come play combating main findings proposed Figure 1. study's have implications our orchestrating immune-evasive programme. expressed adult intestinal epithelium reactivated during tumorigenesis, induces "fetal program" facilitates programme downregulation sensors antigen presentation machinery, akin what embryonic inherently less immunogenic. pre-cancerous exploit foetal-like avoid detection elimination system, thereby promoting initiation progression. identification player CRCs targeting promising strategy enhancing efficacy finding provide direction theoretical basis future clinical applications. While some limitations. One limitations reliance models, fully recapitulate complexity human focus leaves gaps later Subsequent researches incorporate broader range including humanised systems, better mimic disease context. longitudinal studies tracking dynamic changes function throughout entire tumorigenic its summary, groundbreaking research sheds light highlighting target responses enhances immunosuppressive opens avenues therapies disrupt microenvironment. Future should validating these settings exploring SOX17-targeted existing BP: analysed published literature drafted manuscript. HY: contributed figure preparation revision FZ: reviewed edited work supported Natural Science Foundation Enshi Tujia Miao Autonomous Prefecture Government (D20220060), Beijing Bethune Public Welfare (2023-YJ-041-J-005) 2020 annual funding discipline construction, Zhongnan Hospital Wuhan University (YYXKNLJS2024010). authors declare no competing interests. Research data shared.

Language: Английский

Clinical Significance of Multi-Cancer Genome Profiling: Data from a Single Hospital in Japan

Cancer Genomics & Proteomics, Journal Year: 2023, Volume and Issue: 21(1), P. 79 - 87

Published: Dec. 27, 2023

Abstract

Language: Английский