Title:Recent Advances in the Function of the 67 kDa Laminin Receptor and its Targeting for Personalized Therapy in Cancer
Volume: 23
Issue: 32
Author(s): Ada Pesapane, Pia Ragno, Carmine Selleri and Nunzia Montuori*
Affiliation:
- Department of Translational Medical Sciences, University of Naples Federico II, Naples,Italy
Keywords:
Laminin receptor, metastasis, laminin, small molecule, monoclonal antibody, leukemia.
Abstract: The 67 kDa high affinity laminin receptor (67LR) is a non-integrin cell surface receptor for laminin,
the major component of basement membranes. Interactions between 67LR and laminin play a major role in mediating
cell adhesion, migration, proliferation and survival.
67LR derives from homo- or hetero-dimerization of a 37 kDa cytosolic precursor (37LRP), most probably by
fatty acid acylation. Interestingly, 37LRP, also called p40 or OFA/iLR (oncofetal antigen/immature laminin receptor),
is a multifunctional protein with a dual activity in the cytoplasm and in the nucleus. In the cytoplasm,
37LRP it is associated with the 40S subunit of ribosome, playing a critical role in protein translation and ribosome
biogenesis while in the nucleus it is tightly associated with nuclear structures, and bound to components of
the cytoskeleton, such as tubulin and actin.
67LR is mainly localized in the cell membrane, concentrated in lipid rafts. Acting as a receptor for laminin is not
the only function of 67LR; indeed, it also acts as a receptor for viruses, bacteria and prions.
67LR expression is increased in neoplastic cells and correlates with an enhanced invasive and metastatic potential.
The primary function of 67LR in cancer is to promote tumor cell adhesion to basement membranes, the first
step in the invasion-metastasis cascade. Thus, 67LR is overexpressed in neoplastic cells as compared to their
normal counterparts and its overexpression is considered a molecular marker of metastatic aggressiveness in
cancer of many tissues, including breast, lung, ovary, prostate, stomach, thyroid and also in leukemia and lymphoma.
Thus, inhibiting 67LR binding to laminin could be a feasible approach to block cancer progression.
Here, we review the current understanding of the structure and function of this molecule, highlighting its role in
cancer invasion and metastasis and reviewing the various therapeutic options targeting this receptor that could
have a promising future application.
