Introduction

Esophageal squamous cell carcinoma (ESCC) is a common and aggressive malignancy with a rising global incidence, responsible for approximately 544,100 deaths in 2020, thereby posing a significant challenge in oncology (Morgan et al., 2022). The disease is often diagnosed at an advanced stage, limiting therapeutic options and contributing to poor patient prognosis (Lin et al., 2014; Abnet et al., 2018). Although various treatments-including surgery, chemotherapy, and radiotherapy-have been employed, overall survival rates remain unsatisfactory (Nakajima and Kato, 2013; Liao et al., 2019; Doki et al., 2022). This highlights the urgent need to elucidate the molecular mechanisms underlying ESCC pathogenesis to facilitate the development of more effective therapeutic strategies.

The IQ motif-containing GTPase activating protein (IQGAP) family has drawn attention for its complex roles in tumorigenesis (White et al., 2009; Shannon, 2012; Morgan et al., 2019; Wei and Lambert, 2021). Among its members, IQGAP2 is recognized as a key tumor suppressor, involved in regulating cell proliferation, migration, and adhesion (Xie et al., 2019; Xu et al., 2020; Kumar et al., 2021; Song et al., 2023). Several studies have demonstrated that IQGAP2 inhibits cancer cell growth and metastasis through modulation of diverse signaling pathways (Xu et al., 2020; Kumar et al., 2022; Song et al., 2023). Of particular interest is its role in regulating the MEK/ERK mitogen-activated protein kinase (MAPK) pathway, a critical axis in cell growth and survival (Kumar et al., 2021). Although the precise molecular interplay between IQGAP2 and the MEK/ERK MAPK pathway remains under investigation, emerging evidence emphasizes IQGAP2’s importance in maintaining cellular homeostasis and inhibiting tumorigenesis across multiple cancer types (Kumar et al., 2021; Wang et al., 2021; Kumar et al., 2022).

To date, the role of IQGAP2 in ESCC has not been explored. Given its potential therapeutic relevance, this study aims to investigate how reduced IQGAP2 expression influences the MEK/ERK MAPK signaling pathway and promotes ESCC cell proliferation. The findings may offer valuable insights into the molecular pathogenesis of ESCC and suggest IQGAP2 as a potential target for novel therapeutic interventions.