KLK6 regulates ferroptosis through YAP/TAZ in lung adenocarcinoma

The incidence of lung adenocarcinoma (LUAD) has increased in recent years. Kallikrein related peptidase 6 (KLK6), a member of the serine protease family, is found to be aberrantly overexpressed in various solid tumors. This gene functions as a driver of tumor progression, mediating growth, invasion and migration through diverse mechanisms. This study aimed to explore how KLK6 affects the proliferation, invasion, and migration of LUAD by regulating ferroptosis through its influence on Yes-associated protein (YAP) and Transcriptional coactivator with PDZ-binding motif (TAZ), the central transcriptional modules of the Hippo pathway.

We utilized The Cancer Genome Atlas (TCGA) (https://www.cancer.gov/ccg/research/genome-sequencing/tcga) and Western blot analysis to assess KLK6 expression in human LUAD tissues and related cell lines. A series of functional experiments were conducted to explore the impact of KLK6 on the proliferation, invasion, and migration of LUAD. Ferroptosis levels were detected by measuring iron ions, malondialdehyde, JC-1 staining, and Western blot analysis.

KLK6 is highly expressed in LUAD. It promotes the proliferation, invasion, and migration of LUAD and inhibits ferroptosis. Mechanistically, KLK6 affects ferroptosis and the malignant behaviors of LUAD by influencing the interaction between YAP and transcription factors within the Hippo pathway.

The experimental results show that knocking down KLK6 in LUAD inhibits the expression levels of YAP and TAZ in the Hippo pathway and promotes ferroptosis.