Metastatic Tumor Cell-Specific FABP7 Promotes NSCLC Metastasis via Inhibiting β-Catenin Degradation.

Qiaorui Bai,Rong Lian,Shuang Wang,Weizhong Chen,Xia Yang,Quanfeng Li,Han Tian,Yi Yang,Ximeng Liu

doi:10.3390/cells11050805

Qiaorui Bai, Rong Lian + Show 7 more

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https://doi.org/10.3390/cells11050805

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Journal: Cells	Publication Date: Feb 25, 2022
Citations: 5	License type: CC BY 4.0

Affiliation: Sun Yat-sen University, Southern Medical University

Abstract

Metastasis accounts for 90% of cancer-related deaths and represents a prominent malignant feature in non-small cell lung cancer (NSCLC), while tumor cell-specific mechanisms and molecules pivotal for the metastatic capacity remain unclear. By analyzing single-cell RNA sequencing data, we found that fatty acid binding protein 7 (FABP7) was specifically up-regulated in tumor cells of metastatic NSCLC patients and might be a prognostic indicator for poor survival. Experimental studies based on NSCLC cell lines showed that FABP7 promoted the metastatic competencies of NSCLC cells in vitro and in vivo. Mechanistically, we demonstrated that FABP7 was important to canonical Wnt signaling activation and competitively inhibited the interaction between β-catenin and components of its cytoplasmic degradation complex, thereby repressing the phosphorylation-dependent ubiquitination and degradation of β-catenin. Our present study identifies FABP7 as a metastatic tumor cell-specific pro-metastatic gene and uncovers a previously unknown regulatory mechanism underlying Wnt hyperactivation via FABP7-impaired cytoplasmic β-catenin degradation, implicating a novel molecule in regulating NSCLC metastasis.

Highlights

Metastasis accounts for a vast majority of cancer-associated deaths
By analyzing transcriptomic changes in metastatic Non-small cell lung cancer (NSCLC) tumor cells at single-cell resolution in this study, we found that fatty acid binding protein 7 (FABP7) was up-regulated prominently and promoted metastasis-related traits of NSCLC cells
Plasma cells were identified from B cells (Figure S2C), and tumor cells were further identified from cells with epithelial features by the inferCNV algorithm (Figure 1C)

Summary

Introduction

Metastasis accounts for a vast majority of cancer-associated deaths. Non-small cell lung cancer (NSCLC) is the major histopathological subtype of lung cancer with a high metastatic rate of approximately 50% at the time of initial diagnosis [1]. It is not until recent years that single-cell RNA sequencing (scRNA-seq) has been developed and a precise characterization of every type of cell inside the tumor mass can be revealed [6,7,9,10,11,12] By using this technique, a high heterogeneity of either malignant or non-malignant cells in metastatic tumors has been demonstrated, distinct immune or non-immune cell subtypes accounting for metastasis have been identified, and gene signature-based functional indications have been made at the single-cell level in various types of cancers, including NSCLC [6,12,13]. In spite of the above progression, tumor cell-specific molecules and mechanisms regulating NSCLC metastasis remain unclear

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