Work

Deciphering Anticancer Mechanisms of Calycosin in Lung Adenocarcinoma Through Multi-Omics: Targeting SMAD3-Mediated NOTCH Signaling in the Tumor Microenvironment

Year: 2025

Type: article

Abstract: Objective: Lung adenocarcinoma (LUAD) remains a leading cause of cancer-related mortality, particularly in advanced stages. This study investigates the anticancer mechanisms of calycosin, an isoflavonoid derived from Astragalus membranaceus, in LUAD. Methods: Using integrative approaches including bulk and single-cell RNA sequencing, network pharmacology, and molecular docking, we identified SMAD3 as a critical biomarker associated with LUAD staging and prognosis. Results: Calycosin targets SMAD3, modulating the NOTCH signaling pathway in monocytes/macrophages to suppress tumor growth, invasion, and immune evasion. Enrichment analyses revealed significant involvement of NOTCH signaling components in SMAD3-correlated genes, particularly in advanced-stage LUAD. Single-cell RNA sequencing further demonstrated NOTCH pathway enrichment in tumor-associated monocytes/macrophages. Additionally, KMT2A was identified as a key transcriptional regulator in these cells. Conclusions: These findings highlight the potential effects of calycosin and provide novel insights into targeting the tumor–immune microenvironment in LUAD.

Source: Cancers

DOI: 10.3390/cancers17091455

Authors: Bi-Tian Zhang, Xiaoyu Song, Chi-Shing (William) Cho, Chun-Kwok Wong, Dongjie Wang

Institutions: Chinese University of Hong Kong, Harbin Institute of Technology, Queen Elizabeth Hospital, Prince of Wales Hospital, Chinese University of Hong Kong, Shenzhen

Language: English

Topic: Flavonoids in Medical Research

Subfield: Pharmacology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,499