Evidence map›Paper›PMID 42642385›Full record

ArticleNature communications2026

Enzymatic activity-independent NANS stabilizes LATS2 to drive growth and therapeutic resistance in HR+/HER2- breast cancer.

Jia-Yang Cai, Min-Ying Huang, Shao-Ying Yang, Fang-Lin Zhang, Yin-Ling Zhang, Lisa Andriani, Qian Zhao, A-Yong Cao, Da-Qiang Li, Zhi-Ming Shao

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In one paragraph

Article in Nature communications, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
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1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

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3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

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PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors.

Jia-Yang Cai *Department of Breast Surgery, Key Laboratory of Breast Cancer in Shanghai, Fudan University Shanghai Cancer Center, Shanghai, China.
Min-Ying Huang *Cancer Institute, Shanghai Medical College, Fudan University, Shanghai, China.
Shao-Ying YangDepartment of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
Fang-Lin ZhangCancer Institute, Shanghai Medical College, Fudan University, Shanghai, China.ORCID http://orcid.org/0000-0002-5728-0272
Yin-Ling ZhangCancer Institute, Shanghai Medical College, Fudan University, Shanghai, China.
Lisa AndrianiDepartment of Breast Surgery, Key Laboratory of Breast Cancer in Shanghai, Fudan University Shanghai Cancer Center, Shanghai, China.
Qian ZhaoDepartment of Breast Surgery, Key Laboratory of Breast Cancer in Shanghai, Fudan University Shanghai Cancer Center, Shanghai, China.
A-Yong CaoDepartment of Breast Surgery, Key Laboratory of Breast Cancer in Shanghai, Fudan University Shanghai Cancer Center, Shanghai, China. caoayong@fudan.edu.cn.
Da-Qiang LiDepartment of Breast Surgery, Key Laboratory of Breast Cancer in Shanghai, Fudan University Shanghai Cancer Center, Shanghai, China. daqiangli1974@fudan.edu.cn.ORCID http://orcid.org/0000-0002-5113-2332
Zhi-Ming ShaoDepartment of Breast Surgery, Key Laboratory of Breast Cancer in Shanghai, Fudan University Shanghai Cancer Center, Shanghai, China. zhimingshao@fudan.edu.cn.ORCID http://orcid.org/0000-0002-4503-148X

Funding

National Natural Science Foundation of China (National Science Foundation of China) 82372633,82573776
6 · The paper itself

Abstract

Hormone receptor-positive, human epidermal growth factor receptor 2-negative (HR+ /HER2-) breast cancer is the most common subtype in females, frequently challenged by resistance to endocrine therapy and CDK4/6 inhibitors. Here we show that N-acetylneuraminate synthase (NANS) is significantly upregulated in female HR+ /HER2- breast cancer patients, inversely correlating with patient prognosis. Functionally, NANS promotes tumor growth and confers resistance to tamoxifen and CDK4/6 inhibitors independently of its canonical enzymatic activity. Mechanistically, NANS recruits ubiquitin-specific protease 7 (USP7) to deubiquitinate and stabilize large tumor suppressor kinase 2 (LATS2), leading to canonical Hippo pathway activation and upregulation of estrogen receptor α and CDK4. Reintroducing LATS2 into NANS-depleted cells partially rescues the impaired growth-promoting and drug-resistant phenotypes in vitro and in vivo. Furthermore, the clinical relevance of the NANS-USP7/LATS2 axis is confirmed in patient-derived female HR+ /HER2- breast cancer samples. Together, our findings unveil an enzymatic activity-independent role for NANS in driving therapy resistance, nominating it as a promising therapeutic target.

Indexed as

Breast NeoplasmsDrug Resistance, NeoplasmErb-b2 Receptor Tyrosine KinasesProtein Serine-Threonine KinasesTumor Suppressor ProteinsAnimalsCell Line, TumorCell ProliferationFemaleGene Expression Regulation, NeoplasticHumansMiceTamoxifenUbiquitin-Specific Peptidase 7ERBB2 protein, humanErb-b2 Receptor Tyrosine KinasesLATS2 protein, humanProtein Serine-Threonine KinasesTamoxifenTumor Suppressor ProteinsUbiquitin-Specific Peptidase 7

Identifiers

PMID42642385
PMCPMC13507113

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.