Table 1: Summary of SIRT7 and PTEN Interaction Mechanism

Mechanism	Description
Interaction	SIRT7 binds to PTEN, facilitating deacetylation
Deacetylation Site	Lysine 260 (K260)
Ubiquitination	Enhanced via NEDD4L when SIRT7 is active
Outcome	Reduced PTEN levels, increased cancer cell invasion

Estrogen’s Influence on SIRT7 and PTEN in Cancer Progression

Estrogen has been identified as a significant regulator of SIRT7 expression and activity in endometrial cancer. The hormone facilitates the interaction between SIRT7 and PTEN, promoting the degradation of PTEN through a mechanism involving increased acetylation at K260. This estrogen-dependent regulation presents a dual challenge: while estrogen plays a critical role in normal endometrial function and proliferation, its unopposed action can lead to tumorigenesis and progression in susceptible individuals (Hu et al., 2025).

The presence of estrogen leads to a significant decline in PTEN protein levels, underscoring the importance of SIRT7 in mediating estrogen’s pro-tumorigenic effects. The upregulation of SIRT7 in response to estrogen reinforces the notion of a feedback loop that enhances endometrial cancer aggressiveness. Furthermore, patients with high SIRT7 levels and wild-type PTEN exhibit markedly poorer survival outcomes, highlighting the necessity for therapies targeting the SIRT7-PTEN axis (Hu et al., 2025).

SIRT7 and PTEN Interaction: Implications for Metastasis

The interplay between SIRT7 and PTEN has profound implications for the metastatic potential of endometrial cancer. SIRT7’s role in promoting PTEN degradation through deacetylation leads to diminished PTEN activity, which is associated with enhanced epithelial-mesenchymal transition (EMT) and increased migratory capabilities in cancer cells. This mechanism elucidates how SIRT7 contributes to tumor metastasis, particularly in contexts where PTEN remains functionally intact (Hu et al., 2025).

Table 2: Impact of SIRT7-PTEN Interaction on Endometrial Cancer Progression

Factor	Effect on Endometrial Cancer
SIRT7 High Expression	Correlates with poor prognosis
PTEN Degradation	Leads to increased cell migration and invasion
Estrogen Influence	Enhances SIRT7 activity, promoting PTEN loss

Therapeutic Strategies Targeting SIRT7 in Endometrial Cancer

Targeting SIRT7 presents a promising therapeutic avenue for restoring PTEN levels and inhibiting the progression of endometrial cancer. By inhibiting SIRT7 activity, it may be possible to prevent the degradation of PTEN, thereby enhancing its tumor-suppressive functions. This approach could be particularly beneficial for patients who exhibit wild-type PTEN, as they are more likely to respond positively to therapies aimed at reinstating PTEN function (Hu et al., 2025).

Moreover, combination therapies that incorporate SIRT7 inhibitors, alongside existing treatments such as hormonal therapies or chemotherapy, may yield synergistic effects that improve patient outcomes. Given the complex regulatory roles of SIRT7, further research is warranted to identify optimal dosing strategies and therapeutic combinations that could enhance its clinical utility in endometrial cancer management.

Table 3: Potential Therapeutic Approaches Targeting SIRT7

Strategy	Description
SIRT7 Inhibitors	Direct inhibitors to prevent PTEN degradation
Combination Therapies	Use with hormonal or chemotherapeutic agents
Monitoring Biomarkers	Assessing PTEN levels as a response indicator

FAQ

What is the role of SIRT7 in endometrial cancer?

SIRT7 is an NAD+-dependent deacetylase that promotes endometrial cancer progression by regulating the stability and activity of PTEN, a critical tumor suppressor.

How does estrogen influence SIRT7 and PTEN?

Estrogen upregulates SIRT7, which leads to the deacetylation and subsequent degradation of PTEN, thereby facilitating cancer progression.

Why is PTEN important in endometrial cancer?

PTEN acts as a tumor suppressor by regulating cell growth and proliferation. Its loss or inactivation is associated with increased tumor aggressiveness and poor patient outcomes.

What are potential therapeutic strategies targeting SIRT7?

Therapeutic strategies include using SIRT7 inhibitors to restore PTEN levels and employing combination therapies that enhance treatment efficacy in endometrial cancer patients.

How can SIRT7 and PTEN levels be monitored in patients?

Monitoring PTEN levels and SIRT7 activity through imaging and biochemical assays may provide insights into disease progression and therapeutic efficacy.

References

Hu, Z., Tang, M., Huang, Y., Chen, G., & Mao, Z. (2025). SIRT7 facilitates endometrial cancer progression by regulating PTEN stability in an estrogen-dependent manner. Nature Communications, 14(1), 1-15. https://doi.org/10.1038/s41467-025-58317-0
Kobayashi, S., Nakamura, Y., Hashimoto, T., Bando, H., Oki, E., Karasaki, T., … & Hasegawa, K. (2024). Japan society of clinical oncology position paper on appropriate clinical use of molecular residual disease (MRD) testing. International Journal of Clinical Oncology, 29(2), 1-10. https://doi.org/10.1007/s10147-024-02683-0
Cortellesi, E., Savini, I., Veneziano, M., Gambacurta, A., & Catani, M. V. (2025). Decoding the Epigenome of Breast Cancer. International Journal of Molecular Sciences, 26(2), 1-19. https://doi.org/10.3390/ijms26062605