Adipocytes Promote Endometrial Cancer Progression Through Activation of the SIRT1-HMMR Signaling Axis
Contact us if these videos are not relevant.
Contact us if these videos are not relevant.
View abstract on PubMed
Summary
This summary is machine-generated.Adipocytes promote endometrial cancer (EC) via SIRT1 signaling, increasing the oncogene HMMR. Inhibiting SIRT1 may offer a new EC treatment strategy by blocking HMMR and cell cycle progression.
Area Of Science
- Oncology
- Molecular Biology
- Cancer Research
Background
- Adipocytes in omental adipose tissue influence the tumor microenvironment and endometrial cancer (EC) progression.
- The precise mechanisms linking adipocyte-EC interactions to cancer progression remain largely unknown.
Purpose Of The Study
- To elucidate the molecular mechanisms by which adipocyte-EC cell interactions promote endometrial cancer progression.
- To investigate the role of SIRT1 and its downstream effectors in adipocyte-associated EC.
Main Methods
- Co-culture models (in vitro) and xenograft mice models (in vivo) were utilized.
- Immunostaining assessed SIRT1 protein expression in EC patients and normal endometria.
- RNA sequencing identified HMMR as a downstream effector of SIRT1.
- Transient knockdown and chromatin immunoprecipitation assays investigated gene regulation pathways.
Main Results
- Adipocyte-EC cell interaction promoted SIRT1 signaling both in vitro and in vivo.
- SIRT1 expression was significantly higher in EC patients compared to normal endometria.
- SIRT1 inhibition impeded HMMR gene transcription via FOXM1.
- Reduced HMMR expression blocked AURKA activation, leading to cell cycle arrest.
Conclusions
- SIRT1 positively correlates with HMMR in EC tumors, suggesting potential as a biomarker.
- SIRT1 regulates HMMR expression in a FOXM1-dependent manner.
- Interfering with SIRT1 presents a promising therapeutic strategy for endometrial cancer management.
Contact us if these videos are not relevant.
Contact us if these videos are not relevant.
Related Concept Videos
The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
The mammalian target of rapamycin (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast, mTORC2 consists of a...
Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
Every normal cell or tissue is embedded in a complex local environment called stroma, consisting of different cell types, a basal membrane, and blood vessels. As normal cells mutate and develop into cancer cells, their local environment also changes to allow cancer progression. The tumor microenvironment (TME) consists of a complex cellular matrix of stromal cells and the developing tumor. The cross-talk between cancer cells and surrounding stromal cells is critical to disrupt normal tissue...