PO.TB07.02 · 肿瘤生物学
FABP4作为三阴性乳腺癌中一种新型癌干细胞标志物发挥功能
FABP4 functions as a novel cancer stem cell marker in triple-negative breast cancer
作者与单位 Authors & Affiliations
摘要 Abstract
中文摘要
以蒽环类-紫杉醇(A/P)为基础的化疗仍是三阴性乳腺癌(TNBC)的基石。然而，化疗耐药持续损害持久的临床获益。癌干细胞(CSCs)是肿瘤异质性和治疗耐药的主要促成因素。鉴定新型CSC相关基因可能为克服TNBC的耐药提供新策略。对五对配对的TNBC肿瘤及邻近正常组织进行了单细胞RNA测序。与管腔上皮细胞和基底上皮细胞相比，FABP4在CSC样群体中表现出最强的富集。空间转录组学进一步证实了FABP4在CSC富集细胞簇内的表达。整合转录组分析表明，FABP4在紫杉醇耐药的4T1细胞中显著上调，这在4T1和MDA-MB-231细胞的耐药及成球TNBC模型中得到了进一步验证。通过siRNA敲低FABP4显著降低了这些乳腺癌细胞的球体形成能力，支持其在维持TNBC干性中的功能作用。此外，免疫荧光在TNBC临床组织中鉴定出FABP4高表达并伴随CSC标志物，表明其与CSC微环境在空间和生物学上的关联。有必要开展进一步研究以阐明FABP4促进化疗耐药和CSC干性维持的机制通路。
查看英文原文 English abstract
Anthracycline-paclitaxel (A/P)-based chemotherapy remains a cornerstone of triple-negative breast cancer (TNBC). However, chemo-resistance continues to compromise durable clinical benefit. Cancer stem cells (CSCs) are major contributors to tumor heterogeneity and therapeutic resistance. Identifying novel CSC-associated genes may provide new strategies for overcoming drug resistance in TNBC. Single-cell RNA sequencing on five paired TNBC tumors and adjacent normal tissues. FABP4 exhibited the strongest enrichment within the CSC-like population compared with luminal and basal epithelial cells. Spatial transcriptomics further confirmed the expression of FABP4 within CSC-enriched cell clusters. Integrated transcriptome profiling demonstrated significant upregulation of FABP4 in paclitaxel-resistant 4T1 cells, which was further validated in resistant and sphere-forming TNBC models across both 4T1 and MDA-MB-231 cells. Knockdown of FABP4 by siRNA markedly reduced spheroids-forming capacity of these breast cancer cells, supporting its functional role in maintaining the stemness in TNBC. Moreover, FABP4 was identified highly expressed and accompanied by CSC markers in TNBC clinical tissue by immunofluorescence, indicating its spatial and biological association with the CSC niche. Further studies are warranted to elucidate the mechanistic pathways through which FABP4 contributes to chemo-resistance and CSC stemness maintenance.
利益披露 Disclosure
H. Feng, None..
J. Xia, None..
F. Zhong, None..
Y. Cen, None..
L. Jiang, None..
P. Zhao, None..
L. Gao, None..
C. Zou, None.