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Solute carrier family 3 member 2 (SLC3A2), commonly known as the CD98 heavy chain (CD98hc), is a multifunctional type II transmembrane glycoprotein that plays a critical role in cellular metabolism and signaling (Source: UniProt P08195). It serves as an essential chaperone for several light chain amino acid transporters, such as LAT1 (SLC7A5) and LAT2 (SLC7A8), facilitating their stability and trafficking to the plasma membrane to enable the uptake of essential amino acids (Source: PubMed PMID: 21170014). Beyond its transport function, CD98hc interacts with the cytoplasmic domains of integrin beta subunits, thereby modulating signaling pathways involved in cell proliferation, migration, and survival (Source: PubMed PMID: 17635554). In many pathological conditions, particularly solid tumors and inflammatory diseases, CD98hc is significantly overexpressed, making it a valuable prognostic marker and therapeutic target (Source: PubMed PMID: 23835555). Targeting the CD98hc mRNA or protein aims to starve cancer cells of nutrients and disrupt oncogenic signaling, with strategies ranging from monoclonal antibodies like IGN523 to RNA interference technologies (Source: ClinicalTrials.gov NCT02040506).
Inhibition of amino acid transport through LAT1/LAT2 complexes, disruption of integrin-dependent signaling pathways, and induction of antibody-dependent cellular cytotoxicity (ADCC). RNA-targeted approaches utilize antisense oligonucleotides or siRNA to induce degradation of the CD98 heavy chain mRNA, thereby reducing protein expression (Source: PubMed PMID: 23835555).
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