Evidence map›Paper›PMID 34555274›Full record

ArticleCancer communications (London, England)2021

P300/CBP-associated factor (PCAF)-mediated acetylation of Fascin at lysine 471 inhibits its actin-bundling activity and tumor metastasis in esophageal cancer.

Yin-Wei Cheng, Fa-Min Zeng, Da-Jia Li, Shao-Hong Wang, Jian-Zhong He, Zhen-Chang Guo, Ping-Juan Nie, Zhi-Yong Wu, Wen-Qi Shi, Bing Wen and 10 more

Open access · goldAbstract read
In one paragraph

Article in Cancer communications (London, England), 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
2.1field-weighted citation impact, top 14% of its field
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

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

18 citing papers in PubMed, 30 citations in OpenAlex.

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4 · The record

Corrections and comments

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

20 authors at 5 institutions in 1 country.

Yin-Wei ChengThe Key Laboratory of Molecular Biology for High Cancer Incidence Coastal Chaoshan Area, Department of Biochemistry and Molecular Biology, Shantou University Medical College, Shantou, Guangdong, 515041, P. R. China.
Fa-Min ZengThe Key Laboratory of Molecular Biology for High Cancer Incidence Coastal Chaoshan Area, Department of Biochemistry and Molecular Biology, Shantou University Medical College, Shantou, Guangdong, 515041, P. R. China.
Da-Jia LiThe Key Laboratory of Molecular Biology for High Cancer Incidence Coastal Chaoshan Area, Department of Biochemistry and Molecular Biology, Shantou University Medical College, Shantou, Guangdong, 515041, P. R. China.
Shao-Hong WangShantou Central Hospital, Affiliated Shantou Hospital of Sun Yat-sen University, Shantou, Guangdong, 515041, P. R. China.
Jian-Zhong HeThe Key Laboratory of Molecular Biology for High Cancer Incidence Coastal Chaoshan Area, Department of Biochemistry and Molecular Biology, Shantou University Medical College, Shantou, Guangdong, 515041, P. R. China.
Zhen-Chang GuoThe Key Laboratory of Molecular Biology for High Cancer Incidence Coastal Chaoshan Area, Department of Biochemistry and Molecular Biology, Shantou University Medical College, Shantou, Guangdong, 515041, P. R. China.
Ping-Juan NieThe Key Laboratory of Molecular Biology for High Cancer Incidence Coastal Chaoshan Area, Department of Biochemistry and Molecular Biology, Shantou University Medical College, Shantou, Guangdong, 515041, P. R. China.
Zhi-Yong WuShantou Central Hospital, Affiliated Shantou Hospital of Sun Yat-sen University, Shantou, Guangdong, 515041, P. R. China.
Wen-Qi ShiThe Key Laboratory of Molecular Biology for High Cancer Incidence Coastal Chaoshan Area, Department of Biochemistry and Molecular Biology, Shantou University Medical College, Shantou, Guangdong, 515041, P. R. China.
Bing WenThe Key Laboratory of Molecular Biology for High Cancer Incidence Coastal Chaoshan Area, Department of Biochemistry and Molecular Biology, Shantou University Medical College, Shantou, Guangdong, 515041, P. R. China.
Xiu-E XuThe Key Laboratory of Molecular Biology for High Cancer Incidence Coastal Chaoshan Area, Department of Biochemistry and Molecular Biology, Shantou University Medical College, Shantou, Guangdong, 515041, P. R. China.
Lian-Di LiaoThe Key Laboratory of Molecular Biology for High Cancer Incidence Coastal Chaoshan Area, Department of Biochemistry and Molecular Biology, Shantou University Medical College, Shantou, Guangdong, 515041, P. R. China.
Zhi-Mao LiThe Key Laboratory of Molecular Biology for High Cancer Incidence Coastal Chaoshan Area, Department of Biochemistry and Molecular Biology, Shantou University Medical College, Shantou, Guangdong, 515041, P. R. China.
Jian-Yi WuThe Key Laboratory of Molecular Biology for High Cancer Incidence Coastal Chaoshan Area, Department of Biochemistry and Molecular Biology, Shantou University Medical College, Shantou, Guangdong, 515041, P. R. China.
Jun ZhanState Key Laboratory of Natural and Biomimetic Drugs, Peking University Health Science Center, Beijing, 100191, P. R. China.
Hong-Quan ZhangState Key Laboratory of Natural and Biomimetic Drugs, Peking University Health Science Center, Beijing, 100191, P. R. China.
Zhi-Jie ChangSchool of Medicine, Tsinghua University, Beijing, 100084, P. R. China.
Kai ZhangTianjin Key Laboratory of Medical Epigenetics, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, 300070, P. R. China.ORCID 0000-0003-2800-0531
Li-Yan XuThe Key Laboratory of Molecular Biology for High Cancer Incidence Coastal Chaoshan Area, Department of Biochemistry and Molecular Biology, Shantou University Medical College, Shantou, Guangdong, 515041, P. R. China.ORCID 0000-0002-1618-4292
En-Min LiThe Key Laboratory of Molecular Biology for High Cancer Incidence Coastal Chaoshan Area, Department of Biochemistry and Molecular Biology, Shantou University Medical College, Shantou, Guangdong, 515041, P. R. China.ORCID 0000-0001-6375-3614
Shantou University · CNPeking University · CNSun Yat-sen University · CNTianjin Medical University · CNTsinghua University · CN

Funding

2020 Li Ka Shing Foundation Cross-Disciplinary Research Grant 2020LKSFG07BChina Postdoctoral Science Foundation 2018M643134National Cohort of Esophageal Cancer of China 2016YFC0901400National Natural Science Foundation of China 81872372National Natural Science Foundation of China 81902469Natural Science Foundation of China-Guangdong Joint Fund U0932001
6 · The paper itself

Abstract

backgroundFascin is crucial for cancer cell filopodium formation and tumor metastasis, and is functionally regulated by post-translational modifications. However, whether and how Fascin is regulated by acetylation remains unclear. This study explored the regulation of Fascin acetylation and its corresponding roles in filopodium formation and tumor metastasis.

methodsImmunoprecipitation and glutathione-S-transferase pull-down assays were performed to examine the interaction between Fascin and acetyltransferase P300/CBP-associated factor (PCAF), and immunofluorescence was used to investigate their colocalization. An in vitro acetylation assay was performed to identify Fascin acetylation sites by using mass spectrometry. A specific antibody against acetylated Fascin was generated and used to detect the PCAF-mediated Fascin acetylation in esophageal squamous cell carcinoma (ESCC) cells using Western blotting by overexpressing and knocking down PCAF expression. An in vitro cell migration assay was performed, and a xenograft model was established to study in vivo tumor metastasis. Live-cell imaging and fluorescence recovery after photobleaching were used to evaluate the function and dynamics of acetylated Fascin in filopodium formation. The clinical significance of acetylated Fascin and PCAF in ESCC was evaluated using immunohistochemistry.

resultsFascin directly interacted and colocalized with PCAF in the cytoplasm and was acetylated at lysine 471 (K471) by PCAF. Using the specific anti-AcK471-Fascin antibody, Fascin was found to be acetylated in ESCC cells, and the acetylation level was consequently increased after PCAF overexpression and decreased after PCAF knockdown. Functionally, Fascin-K471 acetylation markedly suppressed in vitro ESCC cell migration and in vivo tumor metastasis, whereas Fascin-K471 deacetylation exhibited a potent oncogenic function. Moreover, Fascin-K471 acetylation reduced filopodial length and density, and lifespan of ESCC cells, while its deacetylation produced the opposite effect. In the filipodium shaft, K471-acetylated Fascin displayed rapid dynamic exchange, suggesting that it remained in its monomeric form owing to its weakened actin-bundling activity. Clinically, high levels of AcK471-Fascin in ESCC tissues were strongly associated with prolonged overall survival and disease-free survival of ESCC patients.

conclusionsFascin interacts directly with PCAF and is acetylated at lysine 471 in ESCC cells. Fascin-K471 acetylation suppressed ESCC cell migration and tumor metastasis by reducing filopodium formation through the impairment of its actin-bundling activity.

Indexed as

Esophageal NeoplasmsEsophageal Squamous Cell CarcinomaAcetylationActinsCarrier ProteinsHumansLysineMicrofilament Proteinsp300-CBP-Associated Factorp300-CBP Transcription FactorsProtein Processing, Post-TranslationalActinsCarrier ProteinsfascinLysineMicrofilament Proteinsp300-CBP-Associated Factorp300-CBP Transcription Factorsacetylationactin-bundlingesophageal cancerfascinfilopodium formationP300/CBP-associated factor (PCAF)tumor metastasis

Identifiers

PMID34555274
PMCPMC8696220
OpenAlexW3201380212

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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.