# SCGB3A1‐Epi and KLK10‐Epi Crosstalk With Fibroblasts Promotes Liver Metastasis of Breast Cancer and Pancreatic Ductal Adenocarcinoma

## TL;DR

This study identifies specific cell subtypes in breast cancer and pancreatic cancer that promote liver metastasis and interact with fibroblasts, offering new insights for targeted therapies.

## Contribution

The study identifies SCGB3A1-Epi and KLK10-Epi as key drivers of liver metastasis and reveals their crosstalk with fibroblasts through specific receptor interactions.

## Key findings

- SCGB3A1-Epi and KLK10-Epi are associated with high malignancy and promote liver metastasis in breast cancer and PDAC.
- Ligand-receptor interactions between these epithelial subtypes and fibroblasts, such as CD74-APP and SPP1-CD44, were identified.
- High Fib-11 and CD74 expression correlates with better breast cancer survival, while high SPP1 and CD44 predict worse PDAC outcomes.

## Abstract

The liver often serves as the principal site for metastatic spread from a variety of solid tumors, and metastasis to the liver markedly diminishes patient survival. Single‐cell RNA sequencing (scRNA‐seq) has helped uncover the complexity of liver tumor metastasis. However, the key cellular subtypes of breast cancer and pancreatic ductal adenocarcinoma (PDAC) with liver metastasis and their mechanisms of action are unclear, making treatment difficult.

We used integrated scRNA‐seq data to dissect liver metastasis‐specific epithelial cell subtypes in breast cancer and PDAC, and elucidated their mechanisms through functional analyses and intercellular interactions with fibroblasts.

Interestingly, our results show that SCGB3A1‐Epi and KLK10‐Epi are key drivers of liver metastasis in breast cancer and PDAC, respectively. These subtypes are associated with high malignancy rates and involved in oxidative phosphorylation and other critical pathways. Specific ligand‐receptor interactions were observed between these epithelial subtypes and fibroblasts, with significant interactions between CD74‐APP receptors in SCGB3A1‐Epi and Fib‐11 in breast cancer and between SPP1‐CD44 receptors in KLK10‐Epi and Fib‐11 in PDAC. High expression levels of Fib‐11 and CD74 were correlated with improved survival in breast cancer, whereas high SPP1 and CD44 expression predicted worse PDAC outcomes. Fib‐11 is implicated in signaling pathways associated with tumor metastasis, particularly those involving cell adhesion molecules.

We revealed the cellular heterogeneity of liver metastasis and provided a crucial research foundation for developing novel therapeutic strategies to specifically target metastatic cell subtypes, thereby enhancing patient prognosis.