Cadherins, contact normalization, and targeting podoplanin to treat oral cancer

This project investigates how cadherin-mediated cell contact and the podoplanin (PDPN) receptor influence tumor cell behavior, with a focus on oral squamous cell carcinoma (OSCC). The lab's central interest is how intercellular communication, via junctions and diffusible factors, controls cell growth, differentiation, invasion, metastasis, and inflammation. Building on prior work demonstrating that heterocellular N-cadherin junctions enable nontransformed cells to inhibit the growth of adjacent transformed cells, the Goldberg Lab is exploring mechanisms of contact normalization and how transformed cells escape this growth control. A key finding from the group is that PDPN enables transformed cells to migrate and override cadherin-mediated contact normalization. Independent effects of Src kinase and PDPN on anchorage-independent growth and migration have been described, positioning PDPN as a downstream effector that can promote motility and escape from neighboring cell-mediated suppression.

The Goldberg Lab pursues both mechanistic and translational approaches. Mechanistically, the team examines cadherin junction biology and its impact on oncogenic signaling, including Src kinase-mediated gene expression and protein phosphorylation. Publications from the lab detail how cadherin-mediated contact normalization influences oncogenic Src signaling and how PDPN modulates transformed cell behavior. Translationally, the lab has investigated targeting PDPN to inhibit tumor cell growth and motility. One therapeutic avenue explored is the Maackia amurensis seed lectin (MASL), which the group has shown affects OSCC gene expression and signaling pathways, modifies cell morphology, and influences PDPN expression, viability, and motility. MASL has been studied across in vitro models, in vivo inflammatory disease models, and in a Phase 1 clinical trial evaluating effects on human OSCC cell morphology, PDPN expression, growth, and motility.

The lab's work is documented in numerous peer-reviewed publications and presentations. Recent articles report the environmental control of carcinoma cell expansion, MASL's pleiotropic actions on oral squamous cells, the role of N-cadherin junctions in growth inhibition by nontransformed cells, and the independent contributions of Src and PDPN to malignant phenotypes. Presentations at national and international meetings have emphasized that PDPN enables transformed cells to escape contact normalization and that targeting PDPN can inhibit tumor cell growth and motility. The Goldberg Lab has also presented data on cadherin control of Src-induced motility, the role of junctional communication in contact normalization, and translational findings from the MASL studies, including clinical trial observations.

Collectively, this body of work frames PDPN as a promising therapeutic target to re-establish contact-dependent growth control and limit OSCC progression. By integrating studies of cadherin junction biology, oncogenic kinase signaling, lectin-based modulators like MASL, and early clinical data, the Goldberg Lab aims to translate mechanistic insights about contact normalization into strategies that suppress tumor cell invasion, migration and viability in oral cancer.