MAP7D3, a novel prognostic marker for triple-negative breast cancer, drives cell invasiveness and cancer-initiating cell properties to promote metastatic progression

Biology Direct

Research

Ping-Shen Huang¹  Pei-Yi Chu²  Chen-Chi Wang³  Wen-Hung Kuo³  Shih-Hsuan Chan⁴ 

[1] Department of Nutrition, China Medical University, 40402, Taichung, Taiwan;Department of Post-Baccalaureate Medicine, College of Medicine, National Chung Hsing University, 402, Taichung, Taiwan;School of Medicine, College of Medicine, Fu Jen Catholic University, 242, New Taipei City, Taiwan;Department of Pathology, Show Chwan Memorial Hospital, 500, Changhua, Taiwan;National Institute of Cancer Research, National Health Research Institutes, 704, Tainan, Taiwan;Department of Surgery, National Taiwan University Hospital, 100, Taipei, Taiwan;School of Chinese Medicine, College of Chinese Medicine, China Medical University, 40402, Taichung, Taiwan;Cancer Biology and Precision Therapeutics Center, China Medical University, 40402, Taichung, Taiwan;Chinese Medicine Research Center, China Medical University, 40402, Taichung, Taiwan;

关键词: Triple-negative breast cancer;    Metastasis;    MAP7D3;    Breast cancer-initiating cells.;   

DOI  :  10.1186/s13062-023-00400-x

 received in 2023-06-10, accepted in 2023-07-24,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundPatients with triple-negative breast cancer (TNBC) tend to develop visceral metastasis within five years, making them the most challenging BC patients to treat. The MAP7 protein family is a group of microtubule-binding proteins with a well-known role in microtubule-related cell migration, but its role in metastasis-related properties of TNBC remains unclear.MethodsqRT-PCR and western blot were used to validate mRNA and protein expression of the MAP7 family in the isogenic pairs of TNBC cell lines with low and high metastasis potential. Functional characterization of MAP7D3 was carried out using cell-based and mouse models. The clinical association between MAP7D3 and TNBC was established using datasets in the public domain.ResultsMAP7D3 expression was consistently upregulated in the metastatic subline IV2 and 468-LN at both mRNA and protein levels. Knockdown of MAP7D3 inhibited the 3D colony-forming ability, cell migration, and invasion ability of IV2 and 468-LN, indicating its significant contribution to the metastasis phenotypes. Mechanistically, inhibition of MAP7D3 could significantly increase the sensitivity of metastatic TNBC cells to docetaxel and gemcitabine treatment by reducing the expression of proteins related to breast cancer-initiating cells (BCICs) and drug resistance, as well as suppressing the activity of Rac1. The animal study showed that the depletion of MAP7D3 drastically reduced TNBC tumor growth and impaired the metastatic capability of TNBC cells. Elevated expression of MAP7D3 was found in the metastatic lymph nodes and was significantly associated with advanced stage and higher grade TNBC. Moreover, MAP7D3 expression was significantly correlated with the TNBC population, and its high expression was significantly associated with lymph node metastasis and poor survival outcomes of patients with TNBC.ConclusionOur study indicates that targeting MAP7D3 could be a promising therapeutic strategy for addressing the progression of TNBC, and MAP7D3 may serve as a novel predictive biomarker for the survival outcomes of triple-negative breast cancer.

【 授权许可】

CC BY   
© BioMed Central Ltd., part of Springer Nature 2023

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