National Health Research Institutes

A groundbreaking study by scientists at the Immunology Research Center at the National Health Research Institutes (NHRI) has identified dual-specificity phosphatase 22 (DUSP22) as a key dephosphorylation regulator of the epidermal growth factor receptor (EGFR), a significant oncogenic factor in the development and malignant transformation of lung adenocarcinoma. This discovery opens up possibilities for new precision treatments.

The study was led by Associate Investigator Lin Wen-Jye and its results were published in the Nature-affiliated journal Cell Death Discovery.

DUSP22’s Central Role: DUSP22 acts as a critical gatekeeper in the development and malignant transformation of lung adenocarcinoma. It inhibits lung cancer cell proliferation, survival, and invasion by dephosphorylating and negatively regulating the EGFR and its downstream signaling pathways, thereby preventing tumor progression.

Link to Lung Adenocarcinoma Malignancy: DUSP22 expression is significantly lower in lung adenocarcinoma tissue compared to normal lung tissue. Lower DUSP22 expression correlates with increasing malignancy and poorer patient prognosis, indicating its crucial role in suppressing cancer progression

Regulation Through Dephosphorylation of EGFR: DUSP22 inhibits lung adenocarcinoma cell growth and malignant development through EGFR dephosphorylation. Dysfunction or low expression of DUSP22 can lead to uncontrolled EGFR activation, accelerating cancer progression and reducing patient survival.

DUSP22 Deficiency Induces Dependence on EGFR: DUSP22 inhibits the EGFR tyrosine kinase and its downstream ERK1/2 pathway in lung adenocarcinoma cells. DUSP22-deficient lung adenocarcinoma cells become dependent on EGFR activity, suggesting that EGFR-TKI may be an effective therapeutic strategy for lung adenocarcinomas with low DUSP22 expression. DUSP22 can be used as a predictive biomarker for EGFR-TKI treatment.

Regulation of PD-L1 and c-Met: DUSP22 deletion accelerates EGFR-mutated lung tumor growth and elevates the immune checkpoint molecule PD-L1, facilitating immune evasion. DUSP22 silencing activates c-Met, increasing invasiveness and PD-L1 expression. DUSP22 plays a crucial negative regulatory role in the EGFR/c-Met/PD-L1 pathway.

DUSP22 as a Potential Drug: The study’s experimental evidence shows that DUSP22 can simultaneously inhibit EGFR and ERK1/2 kinases. Overexpression of DUSP22 inhibits the growth of drug-resistant lung adenocarcinoma cells, suggesting that simultaneously inhibiting EGFR and ERK1/2 kinases is a promising strategy for treating drug-resistant lung cancer.

Future Research: The NHRI research team intends to further investigate DUSP22’s role in a larger population of lung adenocarcinoma patients, aiming to translate their findings into novel clinical treatments with a focus on precision medicine.