Cancer Cell Biology

Luca Tamagnone, M.D. PhD
Phone. +39.011.9933204
Fax. +39.011.9933225

Luca Tamagnone
Research topic:
Semaphorins and Semaphorin Receptors in Cancer Progression.

Semaphorins and their receptors (Neuropilins and Plexins), beyond their role in embryo development and morphogenesis, are relevant players in cancer progression and emerging targets for innovative therapeutic approaches. Semaphorins form a conserved family of over 20 members in vertebrates, including transmembrane molecules and secreted members. Secreted semaphorins often act to restrict cell migration; for instance, they can negatively regulate angiogenesis, preventing its pathological role in cancer. Certain semaphorins can play diverse functional roles in different cell populations, due to the involvement of distinctive receptor complexes and signaling cascades. Our lab demonstrated that Sema3A and Sema3E are relevant targets for innovative therapeutic approaches, as they can regulate cancer cells and stromal cells in concomitant manner in the tumor microenvironment. In addition to their role as semaphorin and VEGF receptors, we and others found that neuropilins represent receptor hubs on the cell surface, controlling the function of multiple signaling cascades that support tumor growth, such as EGFR and integrins.

Research achievements:
The laboratory has been working on several aspects of the research topic. We studied the function of Plexin-D1and Neuropilin-1 receptors in cancer cells and in the tumor microenvironment, and found that they can play multiple roles in cancer progression. For instance, oncogene addicted tumor cells use Nrp1 to uphold survival signaling cascades in response to targeted therapies. Moreover, Nrp1 mediates Sema3A-dependent recruitment and localization of tumor associated macrophages in hypoxic tumor areas, where they can deploy their proangiogenic and immune-suppressor activity. Beside secreted family members, transmembrane semaphorins are also currently investigated in the lab, such as Sema4C and Sema6A. We accomplished novel and exciting results about their role in cancer cells, regulating their intrinsic metastatic potential and therapeutic response to targeted therapies. The lab is also a leader in semaphorin research at international level, contributing expert know-how and reagents to frontline collaborative studies.

Conclusions and perspectives:
Semaphorins and their receptors are novel and exciting players in cancer progression. By understanding the specific role of different family members in human cancers, we could validate novel predictive markers of progression or response to innovative targeted therapies. Moreover, certain semaphorins (and receptors) have already been put forward as potential targets for functional interference approaches, aimed at regulating angiogenesis, cancer cell invasiveness, and metastatic progression.

Cancer Cell Biology - Staff

Phone: 011.993.3216
Phone: 011.993.3216
Phone: 011.993.3214
Phone: 011.993.3216
Phone: 011.993.3216 / 3212
Phone: 011.993.3216


Istituto di Candiolo
Strada Provinciale, 142 km 3,95
10060 Candiolo, Torino-Italy


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