# IFIT3 promotes lymph node metastasis by interacting with LASP1 to activate FAK-ERK signaling in esophageal squamous cell carcinoma

## TL;DR

This study shows that IFIT3 promotes lymph node metastasis in esophageal cancer by interacting with LASP1 and activating a key signaling pathway.

## Contribution

The novel finding is that IFIT3 interacts with LASP1 to drive metastasis via the FAK-ERK pathway in ESCC.

## Key findings

- IFIT3 is highly expressed in ESCC, especially in lymph node metastasis tissues.
- IFIT3 promotes ESCC cell metastasis by interacting with LASP1 and activating the FAK-ERK signaling pathway.
- High expression of both IFIT3 and LASP1 is associated with poor prognosis in ESCC patients.

## Abstract

Lymph node metastasis (LNM) is an important cause of poor prognosis in patients with esophageal squamous cell carcinoma (ESCC). However, the mechanism of LNM in ESCC has not been elucidated. Here, we identified interferon-induced proteins with tetratricopeptide repeats 3 (IFIT3) highly expressed in ESCC, especially in LNM tissues. IFIT3 overexpression promoted ESCC cell metastasis in vitro and in vivo. Mechanistically, IFIT3 interacted with LIM and SH3 protein 1 (LASP1) and facilitated the localization of LASP1 to the cell edge, promoting the interaction between LASP1 and Talin1 and the binding of Talin1 to integrin, ultimately activating the FAK-ERK signaling pathway. Clinically, IFIT3 and LASP1 were upregulated in ESCC and LNM tissues and associated with poor prognosis. Moreover, patients with high expression of both IFIT3 and LASP1 have a poorer prognosis. In conclusion, IFIT3 promotes LNM in ESCC through the LASP1/FAK/ERK axis, and IFIT3 is a potential therapeutic target for LNM in ESCC.