STK32C activated IL-6/JAK2/STAT3 signaling and promoted tumor angiogenesis – Nature

Report on the Role of STK32C in Colorectal Cancer Angiogenesis and Implications for Sustainable Development Goal 3 (Good Health and Well-being)

Background: Addressing Non-Communicable Diseases (SDG 3.4)

In alignment with Sustainable Development Goal 3, which aims to ensure healthy lives and promote well-being for all, research into non-communicable diseases such as colorectal cancer (CRC) is paramount. A critical process in CRC progression is angiogenesis, the formation of new blood vessels that supply tumors with nutrients. Understanding the molecular drivers of angiogenesis is essential for developing effective treatments and reducing premature mortality, a key target of SDG 3.4. This report focuses on the serine/threonine kinase STK32C, whose role in this process has been previously undefined.

Methodological Approach

A multi-faceted investigation was conducted to elucidate the function of STK32C in CRC. The methods employed were:

• Clinical Analysis: Examination of STK32C expression in human CRC tissues and its correlation with patient prognosis.
• In Vitro Assays: Evaluation of endothelial cell behaviors, including proliferation, migration, and tube formation, to measure angiogenic activity.
• Mechanistic Investigation: Use of immunoprecipitation, western blotting, and gene set enrichment analysis to determine the molecular pathways involved.
• In Vivo Models: Application of xenograft and Matrigel plug assays to assess the impact of STK32C on tumor growth and angiogenesis in a living system.

Key Findings: Linking STK32C to Cancer Progression

The study yielded several significant results that advance the understanding of CRC and contribute to the goals of SDG 3.

1. STK32C was found to be markedly overexpressed in CRC tissues. This overexpression was strongly associated with poor patient outcomes, identifying it as a significant factor in the burden of this non-communicable disease.
2. Functional assays demonstrated that STK32C overexpression actively promoted angiogenic behaviors in endothelial cells, whereas the knockout of STK32C suppressed these effects.
3. In vivo studies corroborated these findings, showing that the depletion of STK32C led to a reduction in tumor growth, decreased expression of the pro-angiogenic factor VEGF-A, and lower microvessel density within tumors.

Mechanistic Insights and Contribution to Health Innovation (SDG 3)

The research identified a precise molecular mechanism by which STK32C promotes angiogenesis. It was discovered that STK32C directly phosphorylates the STAT3 protein at a specific site, Thr196. This action enhances the binding of STAT3 to JAK2, thereby activating the IL-6/JAK2/STAT3 signaling pathway, a known contributor to cancer progression. This detailed mechanistic insight is a crucial step toward developing targeted therapies, a core component of advancing sustainable and effective healthcare systems as envisioned by SDG 3.

Conclusion: Advancing Cancer Therapy and Global Health Goals

This report concludes that STK32C functions as a pro-angiogenic driver in colorectal cancer by activating the IL-6/JAK2/STAT3 signaling pathway via STAT3 Thr196 phosphorylation. The strong association between STK32C and poor prognosis underscores its potential as both a prognostic biomarker and a novel therapeutic target. The development of anti-angiogenic therapies aimed at inhibiting STK32C could represent a significant advancement in cancer treatment, directly supporting the achievement of Sustainable Development Goal 3 by helping to reduce premature mortality from non-communicable diseases and improve patient well-being worldwide.

Analysis of Sustainable Development Goals (SDGs) in the Article

1. Which SDGs are addressed or connected to the issues highlighted in the article?

• SDG 3: Good Health and Well-being

  The article directly addresses SDG 3, which aims to “ensure healthy lives and promote well-being for all at all ages.” The research focuses on colorectal cancer (CRC), a significant non-communicable disease that contributes to morbidity and mortality worldwide. By investigating the molecular mechanisms of CRC progression and identifying a potential therapeutic target (STK32C), the study contributes to the broader goal of improving health outcomes and combating major diseases.

2. What specific targets under those SDGs can be identified based on the article’s content?

• Target 3.4: Reduce premature mortality from non-communicable diseases

  The article’s content is highly relevant to Target 3.4, which is to “by 2030, reduce by one third premature mortality from non-communicable diseases through prevention and treatment and promote mental health and well-being.” The study’s conclusion highlights STK32C as a “potential biomarker and therapeutic target in anti-angiogenic therapy.” Developing new therapeutic targets is a critical step in improving treatment for colorectal cancer, which would directly contribute to reducing premature deaths caused by this non-communicable disease.

3. Are there any indicators mentioned or implied in the article that can be used to measure progress towards the identified targets?

• Implied Indicators for Target 3.4

  While the article does not mention the official SDG indicator (3.4.1: Mortality rate attributed to cancer), it discusses several related metrics that serve as proxies for measuring progress in cancer treatment and survival. These include:

  1. Patient Prognosis: The article explicitly states that the overexpression of STK32C is “associated with poor outcomes” and has a “strong association with poor prognosis.” Patient prognosis is a direct measure of disease severity and survival likelihood. Improving prognosis through targeted therapies would contribute to reducing cancer mortality.
  2. Tumor Growth: The in vivo experiments assessed “tumor growth.” The finding that “STK32C depletion reduced tumor growth” provides a measurable outcome for the effectiveness of a potential therapy. Reduced tumor growth is a key indicator of successful cancer treatment.
  3. Microvessel Density: The study measured “microvessel density” as an indicator of angiogenesis. The fact that STK32C depletion reduced this density confirms its role in cancer progression. Microvessel density can be used as a biomarker to assess the efficacy of anti-angiogenic therapies, which aim to improve patient outcomes.

4. Summary Table of SDGs, Targets, and Indicators

Source: nature.com