TGF-β signaling in the tumor metabolic microenvironment and targeted therapies

Transforming growth factor-beta (TGF-beta) signaling has a paradoxical role in cancer progression, and it acts as a tumor suppressor in the early stages but a tumor promoter in the late stages of cancer. Once cancer cells are generated, TGF-beta signaling is responsible for the orchestration of the immunosuppressive tumor microenvironment (TME) and supports cancer growth, invasion, metastasis, recurrence, and therapy resistance. These progressive behaviors are driven by an engineof the metabolic reprogramming in cancer. Recent studies have revealed that TGF-beta signaling regulates cancer metabolic reprogramming and is a metabolic driver in the tumor metabolic microenvironment (TMME). Intriguingly, TGF-beta ligands act as anendocrinecytokine and influence host metabolism. Therefore, having insight into the role of TGF-beta signaling in the TMME is instrumental for acknowledging its wide range of effects and designing new cancer treatment strategies. Herein, we try to illustrate the concise definition of TMME based on the published literature. Then, we review the metabolic reprogramming in the TMME and elaborate on the contribution of TGF-beta to metabolic rewiring at the cellular (intracellular), tissular (intercellular), and organismal (cancer-host) levels. Furthermore, we propose three potential applications of targeting TGF-beta-dependent mechanism reprogramming, paving the way for TGF-beta-related antitumor therapy from the perspective of metabolism.

Automated summary

TGF-beta signaling plays a paradoxical role in cancer progression, acting as a tumor suppressor in early stages but a tumor promoter in late stages. It regulates cancer metabolic reprogramming and acts as a metabolic driver in the tumor metabolic microenvironment. Understanding the role of TGF-beta signaling in the tumor metabolic microenvironment is crucial for designing new cancer treatment strategies.