Lactylation-driven TRIM29 induces invasive behavior and lymph node metastasis in gastric cancer via hnRNPA1-mediated Wnt/β-catenin pathway

Sep 22, 2026

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Lactylation of TRIM29 is investigated for its contribution to gastric cancer invasiveness and lymph node metastasis, alongside the impact on 5-fluorouracil-based chemotherapy efficacy. TRIM29 expression and lactylation status are measured in gastric cancer tissues and cell lines, and TRIM29 function is tested by migration, invasion, and tube formation assays. Mechanistically, TRIM29 complexes with hnRNPA1 to activate the Wnt/β-catenin pathway by stabilizing β-catenin through a ubiquitination-dependent mechanism. Targeting TRIM29 and lymphangiogenesis enhances chemotherapy effectiveness in advanced disease.

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[www.nature.com/cddis](www.nature.com/cddis) ARTICLE OPEN Lactylation-drived TRIM29 induces invasive behavior and lymph node metastasis in gastric cancer via hnRNPA1-mediated Wnt/β-catenin pathway Ruheng Hua 1, Jiawei Yu1, Yuanjie Niu 1, Zhenwei Han 1, Boyang Hu 1, Yang Wang 1, Jianwei Zhu 1 ✉ and Qingfeng Ni 1 ✉ © The Author(s) 2026 | | OBJECTIVE: Gastric cancer (GC) is a highly invasive malignancy with a propensity for lymph node metastasis. This study investigated how lactylation of TRIM29 contributes to the invasive behavior of GC and lymph node metastasis and the efﬁcacy of chemotherapy for the disease.
METHODS: We examined the expression levels of TRIM29 and its lactylation status in GC tissues and cell lines using quantitative reverse-transcription polymerase chain reaction, immunohistochemistry based on tissue microarrays and western blotting. Functional transwell migration, three-dimensional invasion assay and tube formation assays were performed to assess the role of TRIM29 in GC. The interaction between TRIM29 and heteronuclear ribonucleoprotein A1(hnRNPA1) was explored by coimmunoprecipitation and mass spectrometry.
RESULTS: Expression of TRIM29 was signiﬁcantly upregulated in GC tissues in comparison with adjacent non-tumor tissues. This upregulation was associated with lymph node metastasis, vascular tumors and a worse prognosis. Lactylation of TRIM29 in GC cells enhanced the migratory ability and invasiveness of these cells and lymph node metastasis. Mechanistically, TRIM29 formed a complex with hnRNPA1, which in turn activated the Wnt/β-catenin signaling pathway by stabilizing β-catenin in a ubiquitinationdependent manner. Targeting TRIM29 and lymphangiogenesis augmented the efﬁcacy of 5-ﬂuorouracil-based chemotherapy. CONCLUSION: Lactylation of TRIM29 promotes invasive behavior and lymph node metastasis in GC cells by engaging the hnRNPA1-mediated Wnt/β-catenin pathway Targeting TRIM29 and lymphangiogenesis may be a promising therapeutic strategy | | | --- | --- | --- | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | .
for patients with advanced GC. | | | | | Cell Death and Disease (2026)17:222; [https://doi.org/10.1038/s41419-026-08468-9](https://doi.org/10.1038/s41419-026-08468-9) | | | | | | INTRODUCTION Gastric cancer (GC), ranking as the ﬁfth most common cancer diagnosis and the ﬁfth highest cause of cancer-related deaths worldwide, poses a substantial threat to global health. Notably, its incidence and mortality rates have shown a signiﬁcant increase in the eastern Asia region, with China being particularly affected [1] . Although surgery is an effective option for some patients with GC, the characteristics of invasive growth and propensity for early metastasis deprive numerous patients of the opportunity for curative resection. The primary sites for metastasis of GC are the lymph nodes and liver, and patients with the disease have a bleak prognosis, with a reported 5-year survival rate of only 5–19%[2, 3] . Therefore, unraveling the intricate mechanisms underlying metastasis of GC is important for developing more precise andefﬁcacious therapeutic approaches. A variety of post-translational modiﬁcation pathways have been documented to modulate the functionality of proteins and the durability of their responses to both internal and external cellular signals [4] . Ubiquitination is a key form of post-translational modiﬁcation in which ubiquitin attaches to target proteins via a series of enzymatic processes, which facilitates the degradation of proteins and upholds the balance of intracellular proteins [5] . Among those, ubiquitin E3 ligase is pivotal in identifying target proteins and sustaining the ubiquitin pathway. Its malfunction can result in the aberrant build-up or over-degradation of substrates, a condition closely associated with the development and adva

FAQs

What is the main objective of this study on gastric cancer?

To determine how lactylation of TRIM29 contributes to invasive behavior, lymph node metastasis, and chemotherapy efficacy in gastric cancer.

How do the researchers assess TRIM29 and its lactylation in gastric cancer?

They measure TRIM29 expression and lactylation status in tissues and cell lines using qRT-PCR, immunohistochemistry on tissue microarrays, and western blotting.

What mechanism links TRIM29 lactylation to metastasis?

TRIM29 forms a complex with hnRNPA1, activating the Wnt/β-catenin pathway by stabilizing β-catenin via a ubiquitination-dependent process.

How does targeting TRIM29 and lymphangiogenesis affect treatment?

Targeting TRIM29 and lymphangiogenesis augments the efficacy of 5-fluorouracil-based chemotherapy for advanced gastric cancer patients.

Sep 22, 2026

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