4F2 cell-surface antigen heavy chain (CD98hc) (CD98hc)

The 4F2 cell-surface antigen heavy chain, also known as CD98hc or SLC3A2, is a multifunctional type II transmembrane glycoprotein that serves as a critical hub linking amino acid metabolism to cellular signaling [1, 2]. It primarily functions as a chaperone for light chain subunits of the SLC7 family, such as LAT1 (SLC7A5) and xCT (SLC7A11), forming heterodimeric complexes that facilitate the transport of essential amino acids and maintain redox homeostasis [4, 14]. Structurally, it consists of a large extracellular domain, a single transmembrane helix, and a short cytoplasmic tail that interacts with beta-integrins to regulate cell adhesion, migration, and survival [7, 11]. In pathological contexts, CD98hc is frequently overexpressed in various malignancies, including head and neck squamous cell carcinoma, gliomas, and prostate cancer, where it correlates with poor prognosis and therapy resistance [6, 16, 20]. It also plays a pivotal role in protecting cells from ferroptosis by stabilizing the xCT cystine/glutamate antiporter [1, 17]. Therapeutic strategies targeting CD98hc include monoclonal antibodies like IGN523 and antibody-drug conjugates (ADCs) such as 19G4-MMAE, which aim to inhibit tumor growth by starving cells of nutrients or disrupting oncogenic signaling [1, 6].

Other names

SLC3A2CD984F2hcMDU14T2HCNACAEFRP-1Solute carrier family 3 member 2Lymphocyte activation antigen 4F2 large subunit

Drugs targeting the 4F2 cell-surface antigen heavy chain primarily act by inhibiting the transport of essential amino acids (e.g., leucine, cystine) to starve metabolically active tumor cells, or by disrupting integrin-mediated signaling pathways that drive cell migration and survival [1, 4]. Additionally, monoclonal antibodies and antibody-drug conjugates (ADCs) can be used to induce antibody-dependent cellular cytotoxicity (ADCC) or deliver potent cytotoxic payloads directly to cells overexpressing the antigen [6, 10].