The receptor protein tyrosine phosphatase PTPRJ negatively modulates the CD98hc oncoprotein in lung cancer cells

Abstract

PTPRJ, a receptor protein tyrosine phosphatase strongly downregulated in human cancer, displays tumor suppressor activity by negatively modulating several proteins involved in proliferating signals. Here, through a proteomic-based approach, we identified a list of potential PTPRJ-interacting proteins and among them we focused on CD98hc, a type II glycosylated integral membrane protein encoded by SLC3A2, corresponding to the heavy chain of a heterodimeric transmembrane amino-acid transporter, including LAT1. CD98hc is widely overexpressed in several types of cancers and contributes to the process of tumorigenesis by interfering with cell proliferation, adhesion, and migration. We first validated PTPRJ-CD98hc interaction, then demonstrated that PTPRJ overexpression dramatically reduces CD98hc protein levels in A549 lung cancer cells. In addition, following to the treatment of PTPRJ-transduced cells with MG132, a proteasome inhibitor, CD98hc levels did not decrease compared to controls, indicating that PTPRJ is involved in the regulation of CD98hc proteasomal degradation. Moreover, PTPRJ overexpression combined with CD98hc silencing consistently reduced cell proliferation and triggered apoptosis of lung cancer cells. Interestingly, by interrogating the can Evolve database, we observed an inverse correlation between PTPRJ and SLC3A2 gene expression. Indeed, the non-small cell lung cancers (NSCLCs) of patients showing a short survival rate express the lowest and the highest levels of PTPRJ and SLC3A2, respectively. Therefore, the results reported here contribute to shed lights on PTPRJ signaling in cancer cells: moreover, our findings also support the development of a novel anticancer therapeutic approach by targeting the pathway of PTPRJ that is usually downregulated in highly malignant human neoplasias.

LncRNA DUXAP8 promotes the progression of laryngeal cancer through targeting miR-384/ POU2F1 axis

“…Prefoldin 4 (PFDN4) is a transcriptional factor that controls the cell cycle and signi cantly upregulated in breast tumor [42]. Protein tyrosine phosphatase receptor type G (PTPRG) is a crucial tumor suppressor in multiple human cancers [43]. Interestingly, we found that knockdown of DUXAP only decreased the expression of POU2F1 and exhibited no obvious change on other candidates, suggesting that DUXAP8 might act as ceRNA of POU2F1.…”

DNA methylation changes related to nutritional deprivation: a genome-wide analysis of population and in vitro data

“…The third DMR identified, CCDC51 , is a protein-coding gene, which is present in endosomes [41]. This gene is involved in several signaling pathways, such as B cell receptor activation [42], micronucleus formation regulation [43], cellular senescence [44], liver-specific microRNA binding [45], and tumor suppressor activity [46], as well as kidney disease [47]. Mouse Ccdc51 gene is the target gene of miR-672-5p, which is highly expressed after steroid-induced osteonecrosis [48].…”

Oncogenic transformation of NIH/3T3 cells by the overexpression of L-type amino acid transporter 1, a promising anti-cancer target

“…Although the major targets of existing anti-cancer therapeutic antibodies are receptortype tyrosine kinases, overexpression of HER1 and HER2 is limited to cancers from squamous [26,27] or glandular [28,29] epithelium, respectively. As CD98/LAT1 is expressed by almost all cancers irrespective of tissue origin [2,3,[30][31][32][33][34][35][36][37][38][39][40], therapeutic antibodies may be ideal against numerous human malignancies. Although clinical trials with anti-CD98hc antibodies were recently started [41], the cancer specificity of LAT1 is superior to that of CD98hc [42][43][44].…”