Iranian journal of immunology : IJISep 30, 2025

Transforming Growth Factor-Beta’s role in balancing cell aging and tumor growth for targeted treatments

Longevity & Aging Weekly Brief ↗PubMed ↗DOI ↗

Updated Jan 19, 2026

Abstract

Transforming growth factor-β (TGF-β) signaling has a dual role in regulating cellular senescence and tumor progression.

In normal tissues, TGF-β acts as a tumor suppressor by controlling the cell cycle and inducing programmed cell death.
Sustained TGF-β signaling in the tumor microenvironment may promote tumor cell growth, spread, and resistance to treatment.
Key factors such as tumor type and cellular environment influence whether TGF-β functions as a suppressor or promoter of tumors.
There are ongoing challenges in targeting TGF-β therapeutically due to its complex roles in cancer.
Emerging precision medicine strategies aim to modulate TGF-β signaling to balance its tumor-suppressive and oncogenic effects.

Simplified

Transforming growth factor-β (TGF-β) signaling plays a complex and dual role in regulating cellular senescence and tumor progression. In normal tissues, TGF-β acts as a tumor suppressor by regulating the cell cycle, inducing apoptosis, and maintaining the integrity of the extracellular matrix (ECM). These functions collectively restrict tumor initiation and support tissue homeostasis. However, in the tumor microenvironment, sustained TGF-β signaling frequently switches to a tumor-promoting role, driving tumor cell proliferation, metastatic dissemination, immune evasion, and therapy resistance. This review aims to clarify the dual role of TGF-β signaling in cellular senescence and tumor progression. It focuses on the molecular mechanisms that drive its transition between tumor suppression and tumor promotion in various biological contexts. We analyze the key determinants governing this functional switch, including tumor type, cellular environment, and signaling crosstalk. Furthermore, we critically evaluate the clinical challenges of therapeutic TGF-β targeting. We highlight emerging strategies to therapeutically modulate TGF-β signaling, focusing on precision medicine approaches that reconcile its tumor-suppressive and oncogenic functions. By providing a comprehensive understanding of TGF-β's dual role, this review offers new insights that may guide personalized cancer therapies and optimize treatment strategies for improved clinical outcomes.

Transforming Growth Factor-Beta’s role in balancing cell aging and tumor growth for targeted treatments

Abstract

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