Reduced S-nitrosylation of TGFβ1 elevates its binding affinity toward the receptor and promotes fibrogenic signaling in the breast
2024

How Reduced S-nitrosylation of TGFβ1 Affects Breast Cancer Signaling

publication Evidence: high

Author Information

Author(s): Letson Joshua, Ren Gang, Zheng Xunzhen, Sweef Osama, Corcino Yalitza Lopes, Furuta Saori

Primary Institution: University of Toledo Health Science Campus

Hypothesis

TGFβ is directly targeted for S-nitrosylation by nitric oxide to suppress its activity.

Conclusion

The study reveals that reduced S-nitrosylation of TGFβ1 increases its binding affinity to the receptor, promoting fibrogenic signaling in breast tissue.

Supporting Evidence

  • Pharmacological inhibition of nitric oxide production in mammary glands led to increased TGFβ activity.
  • Mutations in TGFβ1 cysteines impaired S-nitrosylation and shifted binding affinity towards the receptor.
  • S-nitrosylation-defective mutants showed increased levels of TGFβ signaling molecules.

Takeaway

When a certain chemical in the body is low, a protein called TGFβ1 can become more active, which might lead to problems like cancer.

Methodology

The study involved mutating specific cysteines in TGFβ1 to assess their role in S-nitrosylation and subsequent signaling effects in breast cancer cell lines.

Statistical Information

P-Value

p<0.05

Statistical Significance

p<0.05

Digital Object Identifier (DOI)

10.1016/j.jbc.2024.108011

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