Identification of Nucleolin as a Novel AEG-1-Interacting Protein in Breast Cancer via Interactome Profiling

Abstract

Breast cancer is one of the most common malignant diseases worldwide. Astrocyte elevated gene-1 (AEG-1) is upregulated in breast cancer and regulates breast cancer cell proliferation and invasion. However, the molecular mechanisms by which AEG-1 promotes breast cancer have yet to be fully elucidated. In order to delineate the function of AEG-1 in breast cancer development, we mapped the AEG-1 interactome via affinity purification followed by LC-MS/MS. We identified nucleolin (NCL) as a novel AEG-1 interacting protein, and co-immunoprecipitation experiments validated the interaction between AEG-1 and NCL in breast cancer cells. The silencing of NCL markedly reduced not only migration/invasion, but also the proliferation induced by the ectopic expression of AEG-1. Further, we found that the ectopic expression of AEG-1 induced the tyrosine phosphorylation of c-Met, and NCL knockdown markedly reduced this AEG-1 mediated phosphorylation. Taken together, our report identifies NCL as a novel mediator of the oncogenic function of AEG-1, and suggests that c-Met could be associated with the oncogenic function of the AEG-1-NCL complex in the context of breast cancer.

Ribosome biogenesis in disease: new players and therapeutic targets

“…245 Ncl also binds to telomerase reverse transcriptase (TERT) in the nucleoplasm and promotes its nucleolar localization, preventing cancer cells from senescence and maintaining cancer proliferation. 246 Furthermore, Lee et al 247 showed that Ncl combines with astrocyte-elevated gene-1 in breast cancer to promote the growth and metastasis of breast cancer cells. Increased ribosome biogenesis in cancer cells is closely associated with continuously activated RNA Pol I/III.…”

The Expression of Angiogenesis Genes is Related to Immune Microenvironment and Prognosis of Lung Adenocarcinoma

“…Fibroblast growth factor-binding protein 1(FGFBP1), as an initiating factor of angiogenesis, can bind to broblast growth factor 1 and participate in the process of cell growth together (Tomaszewski et al, 2011). Nucleolin (NCL), an eukaryotic nucleolar phosphoprotein, is aberrantly expressed in a variety of cancers and has received extensive attention (Miranda et al, 2021, Thongchot et al, 2022, Lee et al, 2021. High expression of NCL can not only be used as an indicator of enhanced mitotic activity, but also has anti-apoptotic effects, increasing the proliferation and invasion of tumor cells (Bywater et al, 2013).…”

Mass‐produced gram‐negative bacterial outer membrane vesicles activate cancer antigen‐specific stem‐like CD8+ T cells which enables an effective combination immunotherapy with anti‐PD‐1

“…Protein of OMVs (50 μg) were precipitated by treating methanol/chloroform (Choi et al., 2021). Precipitated proteins were conducted by in‐gel digestion as previously described (S. Lee et al., 2021). The tryptic peptides were analyzed in LC‐MS/MS with Orbitrap Eclipse™ Tribrid™ mass spectrometer (Thermo Fisher Scientific) coupled with Ultimate™ 3000 UHPLC system (Thermo Fisher Scientific).…”