Work

SYT15B promotes tumor progression through interaction with IQGAP1 to activate the MAPK pathway in lung adenocarcinoma

Year: 2025

Type: article

Abstract: Lung adenocarcinoma (LUAD) the predominant subtype of lung cancer, is characterized by rapid tumor growth, local invasion, and distant metastasis. Since dysregulated expression of synaptotagmin (SYT) proteins have been implicated in the development and progression of LUAD, the specific role and mechanisms of SYT15B in LUAD remain unclear. This study demonstrates that elevated SYT15B expression drives malignant progression and predicts poor prognosis in LUAD, as evidenced by integrated clinical sample, in vitro, and in vivo analyses. We identify a novel molecular mechanism whereby SYT15B interacts with IQ motif-containing GTPase-activating protein 1 (IQGAP1), leading to activation of the MAPK signalling pathway and subsequent promotion of aggressive tumor phenotypes. Disruption of the SYT15B-IQGAP1 interaction through IQGAP1 knockdown attenuated MAPK signalling pathway activation and reversed the oncogenic phenotype induced by SYT15B. Notably, specific inhibition of intracellular calcium with BAPTA can also attenuates SYT15B-IQGAP1 complex formation, abrogates MAPK signalling activation, and reverses SYT15B-mediated oncogenic effects. These findings establish the calcium-dependent SYT15B/IQGAP1/MAPK axis as a potential therapeutic and prognostic biomarker in LUAD.

Source: Cellular Signalling

DOI: 10.1016/j.cellsig.2025.112302