Martin E. Hemler, PhD

Dana-Farber Cancer Institute

Academic Titles

Professor, Pathology, Harvard Medical School

Research Program Affiliation

Member, Angiogenesis, Invasion and Metastasis

Member, Cancer Immunology

Research Abstract

My laboratory focuses on novel molecules and pathways that control tumor growth, metastasis and drug resistance. We study a tetraspanin protein, called CD151, that associates with laminin-binding integrins and regulates their contributions to tumor initiation, promotion, progression, invasion and metastasis. Also we have gained new molecular insights into how a novel subpopulation of CD151 supports resistance to many anti-cancer drugs. Also, we have uncovered novel positive and negative regulators of TGF-β signaling. We learned that tetraspanin proteins CD9 and CD81 make vital contributions towards TGF-β1 receptor assembly and signaling. Conversely, the EWI-2 protein associates tightly with CD9 and CD81, thus inhibiting TGF-β1 signaling. These findings have wide implications and provide novel insights into dual roles of TGF-β1 as it inhibits primary tumor growth, but supports EMT, invasion and metastasis. Additionally, we noted that assembly of protein complexes, called tetraspanin-enriched microdomains (TEMS) is facilitated by palmitoylation of tetraspanins, integrins, and other proteins found within TEMS. We learned that palmitoylation of tetraspanin proteins is largely mediated by a palmitoyl acyl transferase called DHHC2, whereas palmitoylation of integrin α6 and β4 subunits is mediated by DHHC3. In further studies of DHHC3, we found that it is a major contributor to tumor growth in vivo, by a mechanism that involves negative regulation of oxidative stress and senescence in tumor cells.