Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2022 Feb 28:13:791272.
doi: 10.3389/fphar.2022.791272. eCollection 2022.

Transforming Growth Factor-Beta (TGF-β) Signaling in Cancer-A Betrayal Within

Abdul Basit Baba  1 , Bilal Rah  1 , Gh Rasool Bhat  1 , Ifra Mushtaq  1 , Sabra Parveen  1 , Rukhsana Hassan  1 , Mahrukh Hameed Zargar  1 , Dil Afroze  1
Affiliations
Review

Transforming Growth Factor-Beta (TGF-β) Signaling in Cancer-A Betrayal Within

Abdul Basit Baba et al. Front Pharmacol. .

Abstract

A ubiquitously expressed cytokine, transforming growth factor-beta (TGF-β) plays a significant role in various ongoing cellular mechanisms. The gain or loss-of-function of TGF-β and its downstream mediators could lead to a plethora of diseases includes tumorigenesis. Specifically, at the early onset of malignancy TGF-β act as tumour suppressor and plays a key role in clearing malignant cells by reducing the cellular proliferation and differentiation thus triggers the process of apoptosis. Subsequently, TGF-β at an advanced stage of malignancy promotes tumorigenesis by augmenting cellular transformation, epithelial-mesenchymal-transition invasion, and metastasis. Besides playing the dual roles, depending upon the stage of malignancy, TGF-β also regulates cell fate through immune and stroma components. This oscillatory role of TGF-β to fight against cancer or act as a traitor to collaborate and crosstalk with other tumorigenic signaling pathways and its betrayal within the cell depends upon the cellular context. Therefore, the current review highlights and understands the dual role of TGF-β under different cellular conditions and its crosstalk with other signaling pathways in modulating cell fate.

Keywords: TGF-β 1; metastasis; signaling pathways; tumor suppressor; tumorigenesis.

PubMed Disclaimer

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Activation of TGF-β signaling by dimerization of respective receptors followed by phosphorylation and translocation of Smads into the nucleus to regulate transcription of genes involved in cell proliferation, apoptosis and differentiation.
FIGURE 2
FIGURE 2
Pharmacological intervention of TFG-β signaling and potential targets Signaling Cross Talk between TGF-β/Smad with other Signaling Pathways.
FIGURE 3
FIGURE 3
A schematic representation of the PI3K/Akt signalling and its downstream targets.
FIGURE 4
FIGURE 4
Activation of NF-kB signaling by phosphorylation of IkB with TLRs and proinflammatory cytokines to release and allow translocation of RelA, p50, RelB into the nucleus to regulate transcription of genes involved in cell proliferation, antiapoptotsis, inflammation, cell survival, innate and adaptive immunity.
FIGURE 5
FIGURE 5
NF-kB activation affects hallmarks of cancer trough the transcription of genes involved in cell proliferation, survival, and angiogenesis.
FIGURE 6
FIGURE 6
Binding of ligand to a cytokine receptor results in dimerization and conformational changes leading to activation of JAK, which in turn phosphorylates downstream mediator STATs thereby allows dimerization followed by translocation into the nucleus to modulate transcription various genes involved in hematopoiesis, immunity, growth and differentiation.
FIGURE 7
FIGURE 7
Crosstalk of TGF-β with other major signaling pathways including PI3K/Akt, NF-kB, and JAK/STAT signaling pathways.
See this image and copyright information in PMC

References

    1. Aashaq S., Batool A., Mir S. A., Beigh M. A., Andrabi K. I., Shah Z. A. (2021). TGF‐β Signaling: A Recap of SMAD‐independent and SMAD‐dependent Pathways. J. Cell Physiol. 237 (1), 59–85. 10.1002/jcp.30529 - DOI - PubMed
    1. Abroun S., Saki N., Ahmadvand M., Asghari F., Salari F., Rahim F. (2015). STATs: an Old story, yet Mesmerizing. Cell J 17, 395–411. 10.22074/cellj.2015.1 - DOI - PMC - PubMed
    1. Ahmed S., Bradshaw A. D., Gera S., Dewan M. Z., Xu R. (2017). The TGF-β/Smad4 Signaling Pathway in Pancreatic Carcinogenesis and its Clinical Significance. J. Clin. Med. 6, 5. 10.3390/jcm6010005 - DOI - PMC - PubMed
    1. Akhurst R. J., Hata A. (2012). Targeting the TGFβ Signalling Pathway in Disease. Nat. Rev. Drug Discov. 11, 790–811. 10.1038/nrd3810 - DOI - PMC - PubMed
    1. Batista I. A. A., Helguero L. A. (2018). Biological Processes and Signal Transduction Pathways Regulated by the Protein Methyltransferase SETD7 and Their Significance in Cancer. Signal. Transduct Target. Ther. 3, 19–14. 10.1038/s41392-018-0017-6 - DOI - PMC - PubMed

LinkOut - more resources