Adipose Tissue Influence on Breast Cancer Progression

Adipose tissue exerts a multifaceted influence on breast cancer progression through direct and indirect interactions within the tumour microenvironment. Mature adipocytes adjacent to tumour cells undergo phenotypic and metabolic reprogramming to become cancer‐associated adipocytes (CAAs), which secrete a repertoire of adipokines, cytokines and extracellular matrix remodelling enzymes. These mediators promote epithelial–mesenchymal transition, local invasion, angiogenesis and metastatic dissemination. Obesity amplifies these processes by increasing adipose mass and chronic inflammation, thus potentiating tumour growth, therapy resistance and poorer clinical outcomes. The interplay between adipocytes, immune cells and cancer cells forms a dynamic signalling network that not only supports primary tumour expansion but also fosters secondary lesion formation and treatment refractoriness across global patient populations.

Research from Nature Portfolio

Recent studies have identified key regulators of adipocyte dedifferentiation and signalling pathways driving the formation of CAAs. Mouse models with dysfunctional adipocytes demonstrate that activation of the YAP/TAZ transcriptional co-activators induces adipocyte dedifferentiation and a malignant microenvironment, whereas pharmacological inhibition of YAP/TAZ restores adipocyte homeostasis and suppresses tumour growth. Complementary work has revealed that adipocyte-derived interleukin-6 activates STAT3 signalling in breast cancer cells, triggering epithelial–mesenchymal transition and enhancing migratory and invasive behaviours. Blockade of the IL-6/STAT3 axis reduces proliferation, migration and invasion, underscoring its potential as a therapeutic target in adipocyte-rich breast tumours.

Adipose Tissue Influence on Breast Cancer Progression publication trend

The graph below shows the total number of articles in adipose tissue influence on breast cancer progression across all publications each year (not limited to Nature Index journals).

Technical terms

Adipocyte: A cell specialised for lipid storage within adipose tissue.

Cancer‐associated adipocyte (CAA): An adipocyte reprogrammed by tumour cells to support malignancy.

Adipokine: A bioactive molecule secreted by adipose tissue influencing metabolism and cell signalling.

YAP/TAZ signalling: Transcriptional regulators involved in mechanotransduction and cell proliferation.

Epithelial–mesenchymal transition (EMT): A cellular programme enabling epithelial cells to acquire migratory and invasive traits.

SERPINE1: A protease inhibitor implicated in extracellular matrix remodelling and DNA repair facilitation.

Major vault protein (MVP): A cytosolic protein forming vault particles that mediate drug efflux.

PLOD2: An enzyme catalysing collagen crosslinking, promoting matrix stiffening and invasion.

References

1. Dysfunctional adipocytes promote tumor progression through YAP/TAZ-dependent cancer-associated adipocyte transformation. Nature Communications (2024).
2. Interleukin-6/STAT3 signalling regulates adipocyte induced epithelial-mesenchymal transition in breast cancer cells. Scientific Reports (2018).
3. Obesity promotes radioresistance through SERPINE1-mediated aggressiveness and DNA repair of triple-negative breast cancer. Cell Death & Disease (2023).
4. Adipocytes promote breast cancer resistance to chemotherapy, a process amplified by obesity: role of the major vault protein (MVP). Breast Cancer Research (2019).
5. Adipocyte-derived IL-6 and leptin promote breast Cancer metastasis via upregulation of Lysyl Hydroxylase-2 expression. Cell Communication and Signaling (2018).