Adipocyte-driven STAT3-ANGPT2-PTGIS axis promotes cutaneous metastasis in breast cancer and represents a targetable...

Area of Science:

• Oncology
• Dermatology
• Molecular Biology

Background:

• Cutaneous metastatic breast cancer (CMBC) is an aggressive malignancy with limited research, posing a significant clinical challenge.
• Tumor adaptation to the skin microenvironment drives CMBC progression, necessitating a deeper understanding of its mechanisms.

Purpose of the Study:

• To investigate the molecular mechanisms underlying CMBC progression.
• To identify potential therapeutic targets for CMBC.

Main Methods:

• Transcriptomic profiling of CMBC.
• Functional assays and mouse models to study metastasis.
• Pharmacologic inhibition of key signaling pathways.

Main Results:

• CMBC is linked to poor prognosis, increased angiogenesis, inflammation, and altered lipid metabolism (arachidonic and linoleic acid pathways).
• Adipocyte-derived signals promote cutaneous metastasis via STAT3 activation, upregulating Angpt2, Vegfc, and Ptgis.
• STAT3 inhibition effectively suppressed CMBC metastasis in vitro and in vivo.
• Elevated STAT3, ANGPT2, and PTGIS levels correlate with reduced patient survival.

Conclusions:

• STAT3-mediated signaling and metabolic reprogramming are critical drivers of CMBC progression.
• Targeting STAT3 presents a promising therapeutic strategy for CMBC.
• Further research into CMBC pathogenesis is crucial for improving patient outcomes.