Hyaluronan mediated motility receptor (HMMR) (HMMR)

HMMR (Hyaluronan Mediated Motility Receptor), also known as RHAMM (Receptor for Hyaluronan-Mediated Motility), is a versatile protein that functions both as a cell surface receptor and an intracellular spindle-associated protein [2, 3, 7]. It plays a critical role in regulating cell motility, proliferation, and mitotic spindle integrity by interacting with hyaluronan and various intracellular partners like dynein and BRCA1 [1, 6, 15]. While its expression is restricted in normal adult tissues to the testis, placenta, and thymus, HMMR is frequently overexpressed in a wide range of malignancies, including breast, prostate, and lung cancers [1, 2, 11]. This overexpression is strongly associated with increased tumor invasiveness, metastasis, and poor patient prognosis, making it a valuable biomarker for risk stratification [2, 7, 10]. Therapeutic approaches targeting HMMR include peptide-based vaccines, such as the RHAMM-R3 vaccine, and small molecules like 4-methylumbelliferone that inhibit hyaluronan-mediated signaling [2, 14, 16]. Additionally, experimental HA-mimetic peptides have shown promise in inducing apoptosis in cancer cells by competitively inhibiting hyaluronan binding [9]. Despite its potential as a therapeutic target, the structural complexity of HMMR and its diverse subcellular localization present significant challenges for the development of highly specific inhibitors [2, 15]. Its involvement in normal physiological processes like wound healing and brain development also necessitates careful consideration of safety and off-target effects [6, 7].

Other names

RHAMMCD168IHABPReceptor for hyaluronan-mediated motilityIntracellular hyaluronic acid-binding protein

Drugs targeting HMMR primarily work through competitive inhibition of hyaluronan binding, inhibition of hyaluronan synthesis, or by inducing a T-cell mediated immune response against RHAMM-expressing cells [2, 7, 9, 14].