2022,
BMC Cancer.
DOI:
10.1186/s12885-022-09877-7
Cancer-associated fibroblasts strengthen cell proliferation and EGFR TKIs resistance through aryl hydrocarbon receptor dependent signals in non-small cell lung cancer
Hao Feng
, Boxiong Cao
, Xuan Peng
, Qiang Wei
Abstract:
Abstract The tumor microenvironment is a dynamic cellular milieu that interacts with cancer cells and promotes tumor progression and metastasis. However, the specific mechanisms by which the tumor microenvironment impacts cancer cells’ behaviors remain poorly understood. In this study, enriched cancer-associated fibroblasts (CAFs) were observed in tumor tissues isolated from epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKIs) resistant non-small cell lung cancer (NSCLC) patients. CAFs isolated from tumor tissues were capable of producing tryptophan metabolite kynurenine (Kyn), which significantly increased the proliferation and EGFR TKIs resistance of NSCLC cells. In this study, it was further observed that the activation of tryptophan 2,3-dioxygenase (TDO) in CAFs, resulted in the enhanced capability of tryptophan metabolism in them compared to normal fibroblasts. As a result, Kyn produced by CAFs facilitated the up-regulation of Aryl Hydrocarbon Receptor (AhR) signals in NSCLC, thereby resulting in the downstream ATK and ERK signaling pathways activation. Finally, inhibition of AhR signals efficiently prevented tumor growth and development of EGFR TKIs resistance, eventually improved the outcome of EGFR TKIs, and described a promising therapeutic strategy for NSCLC.
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2023-02-05 17:58:00
龙海晨:
#paper Feng H, Cao B, Peng X, Wei Q. Cancer-associated fibroblasts strengthen cell proliferation and EGFR TKIs resistance through aryl hydrocarbon receptor dependent signals in non-small cell lung cancer. BMC Cancer. 2022 Jul 13;22(1):764. doi: 10.1186/s12885-022-09877-7. PMID: 35831824; PMCID: PMC9281029.文章属于研究肿瘤的领域。进一步描述了CAF在癌症EGFR-TKIs耐药性发展中的作用。阐述了CAF与EGFR TKIs耐药相关的潜在机制，其依赖于Kyn/AhR/AKT/ERK信号通路。阻断AhR可有效改善EGFR TKIs的结果，为临床治疗癌症提供了一种新的策略。