Abstract IA33: Regulation of TGF-{beta} receptor signaling in cancer

TGF-β plays a crucial role during development and in maintaining tissue homeostasis. Perturbation in signaling via TGF-β type I and type II serine/threonine kinase receptors and intracellular SMAD transcriptional effectors, can lead to a large variety of diseases, including cancer. TGF-β has a dual role in cancer progression. During the early phase, TGF-β acts as a tumor suppressor, exemplified by deletions or mutations in the core components of the TGF-β signaling pathway. In late phase, TGF-β promotes processes that support tumor progression such as tumor cell invasion, dissemination, and immune evasion. Clinical trials for the treatment of cancer patients using systemic TGF-β signaling inhibitors have been initiated. These agents target TGF-β ligand or TGF-β receptor and inhibit all responses, and may have unwanted on-target effects. I will present our efforts to identify new druggable regulators of TGF-β signaling, which may allow for a more selective antagonism of the tumor promoting pathways by TGF-β. For example, E3 ubiquitin ligase TRAF4 and deubiquitinating enzyme USP4 - that are highly expressed in breast cancer - regulate the stability of specific TGF-β signaling components and thereby promote TGF-β-induced breast cancer cell invasion and metastasis.Citation Format: Peter ten Dijke. Regulation of TGF-β receptor signaling in cancer. [abstract]. In: Proceedings of the AACR Special Conference: Devel...
Source: Molecular Cancer Research - Category: Cancer & Oncology Authors: Tags: Signaling Pathways: BMP/TGFbeta/SMAD: Oral Presentations - Invited Abstracts Source Type: research