UBC9-mediated SUMOylation of CORO1C drives lung adenocarcinoma progression via Arp2/3-dependent cytoskeletal remodeling

Sep 22, 2026

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Lung adenocarcinoma (LUAD) remains a major cause of cancer mortality, and improving outcomes requires clearer molecular drivers. SUMOylation is a reversible post-translational modification in which UBC9 conjugates SUMO to lysine residues, yet LUAD-specific substrates and roles of UBC9 are insufficiently defined. UBC9 is elevated in LUAD and high expression predicts worse clinical outcomes. Genetic loss of UBC9 suppresses proliferation, migration, invasion, and tumorigenesis in vitro and in vivo. CORO1C is identified as a UBC9 SUMOylation substrate, and its SUMOylation enhances Arp2 complex binding, remodels actin cytoskeleton, and promotes malignant behaviors.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages13

Reading Time33 min

AccessFree to download

Introduction

Lung adenocarcinoma background and clinical need

Post-translational modifications and SUMOylation pathway

Results

UBC9 expression and clinical relevance in LUAD

Functional role of UBC9 in LUAD progression

Identification of CORO1C as a SUMOylation substrate

Mechanism: CORO1C SUMOylation, Arp2 complex binding, and actin remodeling

Discussion

[www.nature.com/cddis](www.nature.com/cddis) ARTICLE OPEN UBC9-mediated SUMOylation of CORO1C drives lung adenocarcinoma progression via Arp2/3-dependent cytoskeletal remodeling Zhe Zhang 1,2,3,4, Bing Xiao5, Yupeng Jiang6, Lixia Niu4,7, Li Wang 1,2,3,4 ✉ and Juan Cai 4,7 ✉ © The Author(s) 2026 | | | | | --- | --- | --- | | | Lung adenocarcinoma (LUAD) remains a leading cause of cancer-related mortality worldwide, and understanding its molecular drivers is critical for improving therapeutic outcomes. SUMOylation is a form of post-translational modiﬁcation that conjugates small ubiquitin-like modiﬁer (SUMO) to speciﬁc lysine residues of target proteins. The sole SUMO E2-conjugating enzyme UBC9 is upregulated in multiple malignancies, yet its functional role and speciﬁc substrate in LUAD remain poorly deﬁned. Here, we demonstrate that UBC9 is signiﬁcantly elevated in LUAD tissues, and its high expression is associated with adverse clinic outcomes. Functional assays revealed that genetic ablation of UBC9 robustly suppresses LUAD cell proliferation, migration, invasion, and tumorigenesis both in vitro and in vivo. Through immunoprecipitation-mass spectrometry, we identiﬁed Coronin-1C (CORO1C), a master regulator of actin dynamics, as a key substrate of UBC9-mediated SUMOylation. Mechanistically, SUMOylation of CORO1C atlysine residues K19, K311, and K440 enhances its binding to actin-related protein 2 (Arp2) complex, promotes actin‑based cytoskeletal remodeling, and drives malignant cellular behaviors. Collectively, our work reveals a previously unrecognized regulatory axis in which UBC9‑dependent SUMOylation licenses CORO1C to orchestrate Arp2/3‑mediated cytoskeletal dynamics, thereby advancing LUAD progression. These ﬁndings reveal CORO1C as a novel SUMOylation target in lung adenocarcinoma and offer new mechanistic insights into tumor cell motility, but also highlight a promising therapeutic avenue for treating | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | advanced LUAD. | | | | Cell Death and Disease (2026)17:434; [https://doi.org/10.1038/s41419-026-08653-w](https://doi.org/10.1038/s41419-026-08653-w) | | | | | | INTRODUCTION Lung cancer represents the foremost cause of cancer-related mortality worldwide, accounting for approximately 18% of total cancer deaths according to recent global estimates [1, 2] . Histologically, it is broadly categorized into small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC), with NSCLC comprising about 85% of all cases [3, 4] . Among NSCLC subtypes, lung adenocarcinoma (LUAD) is the most prevalent form, characterized by distinct pathological and molecular features [5] . Despite signiﬁcant advancements in clinical management, including the development of targeted therapies such as tyrosine kinase inhibitors, the prognosis for LUAD patients remains suboptimal, with a persistently modest 5-year survival rate [6, 7] . This poor prognosis underscores the urgent need to elucidate the underlying molecular mechanisms driving LUAD progression. Post-translational modiﬁcations (PTMs) are essential regulators of diverse cellular processes, modulating protein-protein interactions, transcriptional regulation, subcellular trafﬁcking, and protein stability [8] . Among these, SUMOylation, a dynamic and reversible covalent attachment of Small Ubiquitin-like Modiﬁer (SUMO) proteins to target substrates, has garnered increasing attention for its pivotal role in oncogenesis [9] . The SUMOylation cascade is orchestrated by E1-activating enzymes SAE1/SAE2, E2-conjugating enzyme UBC9 (coding by the UBE2I gene), and E3 ligases [10–12] . Conversely, de-SUMOylation is mediated by a family of Sentrin/ SUMO-speciﬁc proteases (SENPs), with SENP1 being the principal de-SUMOylated protease in mammalian cells [13] . UBC9, as the sole E2 enzyme, is indispensable for SUMOylation, an

FAQs

What role does UBC9 play in lung adenocarcinoma progression?

UBC9 is significantly elevated in LUAD tissues, and its high expression correlates with adverse clinical outcomes. Genetic ablation of UBC9 suppresses LUAD cell proliferation, migration, invasion, and tumorigenesis in vitro and in vivo.

How was CORO1C identified in this study?

Immunoprecipitation-mass spectrometry identified Coronin-1C (CORO1C) as a key substrate of UBC9-mediated SUMOylation.

What is the mechanistic link between CORO1C SUMOylation and cytoskeletal remodeling?

SUMOylation of CORO1C at specific lysine residues enhances its binding to the Arp2 complex, promoting actin-based cytoskeletal remodeling. This remodeling drives malignant cellular behaviors and advances LUAD progression.

Sep 22, 2026

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