4.7 Article

Hypoxia-Mediated Complement 1q Binding Protein Regulates Metastasis and Chemoresistance in Triple-Negative Breast Cancer and Modulates the PKC-NF-κB-VCAM-1 Signaling Pathway

期刊

出版社

FRONTIERS MEDIA SA
DOI: 10.3389/fcell.2021.607142

关键词

hypoxia; TNBC; C1QBP; metastasis; chemoresistance

资金

  1. Heilongjiang Health and Family Planning Commission Foundation [2019-056]
  2. Haiyan Fund Project of Harbin Medical University Cancer Hospital [JJQN 201806]
  3. National Natural Science Foundation of China [81972706, 81602639, 81872149]
  4. Heilongjiang Postdoctoral Foundation [LBH-Z18222]

向作者/读者索取更多资源

This study found that hypoxia-induced HIF-1 alpha upregulated C1QBP, which when inhibited, notably blocked the metastasis of TNBC cells and increased their sensitivity to PTX under hypoxic conditions. Depletion of C1QBP decreased VCAM-1 expression by reducing the amount of P65 in the nucleus and suppressed the activation of hypoxia-induced PKC-NF-kappa B signaling. Targeting C1QBP along with PTX treatment could be a potential treatment for TNBC patients.
Objectives Complement 1q binding protein (C1QBP/HABP1/p32/gC1qR) has been found to be overexpressed in triple-negative breast cancer (TNBC). However, the underlying mechanisms of high C1QBP expression and its role in TNBC remain largely unclear. Hypoxia is a tumor-associated microenvironment that promotes metastasis and paclitaxel (PTX) chemoresistance in tumor cells. In this study, we aimed to assess C1QBP expression and explore its role in hypoxia-related metastasis and chemoresistance in TNBC. Materials and Methods RNA-sequencing of TNBC cells under hypoxia was performed to identify C1QBP. The effect of hypoxia inducible factor 1 subunit alpha (HIF-1 alpha) on C1QBP expression was investigated using chromatin immunoprecipitation (ChIP) assay. The role of C1QBP in mediating metastasis, chemoresistance to PTX, and regulation of metastasis-linked vascular cell adhesion molecule 1 (VCAM-1) expression were studied using in vitro and in vivo experiments. Clinical tissue microarrays were used to verify the correlation of C1QBP with the expression of HIF-1 alpha, VCAM-1, and RELA proto-oncogene nuclear factor-kappa B subunit (P65). Results We found that hypoxia-induced HIF-1 alpha upregulated C1QBP. The inhibition of C1QBP notably blocked metastasis of TNBC cells and increased their sensitivity to PTX under hypoxic conditions. Depletion of C1QBP decreased VCAM-1 expression by reducing the amount of P65 in the nucleus and suppressed the activation of hypoxia-induced protein kinase C-nuclear factor-kappa B (PKC-NF-kappa B) signaling. immunohistochemistry (IHC) staining of the tissue microarray showed positive correlations between the C1QBP level and those of HIF-1 alpha, P65, and VCAM-1. Conclusion Targeting C1QBP along with PTX treatment might be a potential treatment for TNBC patients.

作者

我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。

评论

主要评分

4.7
评分不足

次要评分

新颖性
-
重要性
-
科学严谨性
-
评价这篇论文

推荐

暂无数据
暂无数据