High-Glucose Fuel for Breast Cancer? Absin Decodes the RCC2-Lactylation Switch

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January 06, 2026

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As the most prevalent malignancy in women, breast cancer incidence continues to rise. The causal links between dietary sugars, metabolic reprogramming and tumorigenesis remain an intense focus of research. Now, a cutting-edge study in Advanced Science unveils the first evidence that high-glucose-induced lactylation of RCC2 fuels breast-cancer proliferation, while Absin’s flagship reagents provide the enabling technology to decode the mechanism.

Title: High Sugar Induced RCC2 Lactylation Drives Breast Cancer Tumorigenicity Through Upregulating MAD2L1

Journal: Advanced Science (IF 14.1) | DOI: https://doi.org/10.1002/advs.202415530

Absin products used: IP/Co-IP Kit (abs955), Organotial Human Breast-Cancer Organoid Culture Kit (abs9446)

I. Conceptual framework: tracing the “high-glucose → lactate → proliferation” axis

Central hypothesis

High dietary glucose boosts tumor glycolysis, elevates extracellular lactate, and increases global protein lactylation. Whether lactylation links metabolic flux to MAD2L1 up-regulation and mitotic drive in breast cancer was unknown.

Logic pipeline

Verify that high glucose raises lactate levels and MAD2L1 expression;
Identify the lactylated scaffold protein coupling metabolism to MAD2L1 (RCC2);
Map the lactylation site (K124) and the responsible acyl-transferase (KAT2A);
Elucidate how RCC2-lactylation stabilizes MAD2L1 mRNA via SERBP1;
Exploit the pathway therapeutically with a small-molecule RCC2-lactylation inhibitor.

II. Major breakthroughs: four milestones pointing to new therapeutics

1. High-glucose → lactate → MAD2L1 axis is essential for breast-cancer growth

High-glucose culture increased global lactylation and MAD2L1 protein (Fig. 1B/C). Tumor size positively correlated with tissue lactylation (Table 1). Silencing MAD2L1 abolished lactate-induced proliferation (Fig. 1H–J), establishing MAD2L1 as the critical downstream effector.

2. RCC2 is the principal lactylation substrate linking metabolism to MAD2L1

IP–MS identified RCC2 as a heavily lactylated protein (Fig. 2D-E). RCC2 and MAD2L1 expression were tightly correlated. RCC2 over-expression up-regulated MAD2L1, whereas RCC2 silencing reversed lactate-mediated induction of MAD2L1 and proliferation (Fig. 2B–C, G–I).

3. KAT2A lactylates RCC2 at K124, enhancing SERBP1 recruitment

Truncation mutagenesis and LC-MS pinpointed K124 as the conserved lactylation site (Fig. 3B–C, E). KAT2A was identified as the acyl-transferase catalyzing RCC2-K124-lactylation (Fig. 3F–G, K). Lactylation strengthened RCC2–SERBP1 association and promoted nuclear translocation of SERBP1 (Fig. 6F–J).

4. SERBP1 stabilizes MAD2L1 mRNA; SBDA blocks RCC2 lactylation and tumor growth

RIP confirmed SERBP1 binding to the 3′UTR of MAD2L1 mRNA, prolonging its half-life (Fig. 5A–D). RCC2-K124-lactylation was obligatory for this interaction (Fig. 5E). In-silico screening yielded SBDA, a small molecule occupying the RCC2-K124 pocket, which inhibited lactylation, reduced MAD2L1, and suppressed tumor growth in cells and patient-derived organoids (Fig. 7E–H).

III. Powered by absin: robust tools for decisive assays

Two absin products underpinned the mechanistic dissection:

Product 1: IP/Co-IP Kit (cat. abs955)

Applications

Detection of endogenous RCC2 lactylation (Fig. 2D): IP of RCC2 followed by Pan-Kla immunoblot;
Validation of RCC2–SERBP1 interaction (Figs. 4G–H, 6F–G);
Confirmation of KAT2A–RCC2 binding (Figs. 3H–I).

Key merits

Protein A/G magnetic beads deliver high binding capacity and low non-specific adsorption, ensuring clean inputs for downstream WB or MS.

Product 2: Organotial Human Breast-Cancer Organoid Culture Kit (cat. abs9446)

Applications

Provided high-purity, genetically stable organoids for SBDA efficacy testing (Fig. 7H), bridging 2-D cultures and in-vivo models.

IV. Conclusions & perspectives

The study delineates a complete pathway: high glucose → lactate → KAT2A-mediated RCC2-K124 lactylation → SERBP1 nuclear import → MAD2L1 mRNA stabilization → breast-cancer proliferation (Fig. 7I). Small-molecule SBDA disrupts this oncogenic circuit, offering a tractable therapeutic avenue for sugar-associated breast cancers.

absin will continue to develop precise, user-friendly tools that empower researchers to unravel complex molecular networks and accelerate the translation of metabolic interventions into clinical benefit.

This summary is based on the open-access article published in Advanced Science (DOI: 10.1002/advs.202415530). All original figures and data are the intellectual property of the journal and the authors. If any infringement is suspected, please contact us for immediate removal; we will cooperate promptly and assume no legal liability.

Cat. #	Product	Size
abs955	Immunoprecipitation (IP/CoIP) kit	50T
abs9446	Human Breast Cancer Organoid Culture Medium Kit	1kit
abs9649	Protein A/G Magnetic IP/Co-IP Kit	10T/50T
abs50034	ChIP Kit	22T
abs50074	DNA Pull Down Kit(Animal)	6T
abs50072	RNA Pull Down Kit	6T

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