AKT serine/threonine kinase 2-mediated phosphorylation of fascin threonine 403 regulates esophageal cancer progression.

Actins / metabolism Carrier Proteins Cell Line, Tumor Esophageal Neoplasms / genetics Humans Microfilament Proteins Phosphorylation Proto-Oncogene Proteins c-akt / metabolism Serine / metabolism Threonine / metabolism
AKT serine/threonine kinase 2 Cell migration Esophageal cancer Fascin Filopodia Phosphorylation

Journal

The international journal of biochemistry & cell biology
ISSN: 1878-5875
Titre abrégé: Int J Biochem Cell Biol
Pays: Netherlands
ID NLM: 9508482

Informations de publication

Date de publication:
04 2022
Historique:
received: 26 11 2021
revised: 20 02 2022
accepted: 21 02 2022
pubmed: 28 2 2022
medline: 6 5 2022
entrez: 27 2 2022
Statut: ppublish

Résumé

Fascin is the main actin-bundling protein in filopodia and is highly expressed in metastatic tumor cells. The overexpression of Fascin has been associated with poor clinical prognosis and metastatic progression. Post-translational modifications of Fascin, such as phosphorylation, can affect the proliferation and invasion of tumor cells by regulating the actin-bundling activity of Fascin. However, the phosphorylation sites of Fascin and their corresponding kinases require further exploration. In the current study, we identified novel phosphorylation of Fascin Threonine 403 (Fascin-T403) mediated by AKT serine/threonine kinase 2 (AKT2), which was studied using mass spectrometry data from esophageal cancer tissues (iProX database: IPX0002501000). A molecular dynamics simulation revealed that Fascin-Threonine 403 phosphorylation (Fascin-T403D) had a distinct spatial structure and correlation of amino acid residues, which was different from that of the wild type (Fascin-WT). Low-speed centrifugation assay results showed that Fascin-T403D affected actin cross-linking. To investigate whether Fascin-T403D affected the function of esophageal cancer cells, either Fascin-WT or Fascin-T403D were rescued in Fascin-knockout or siRNA cell lines. We observed that Fascin-T403D could suppress the biological behavior of esophageal cancer cells, including filopodia formation, cell proliferation, and migration. Co-immunoprecipitation (Co-IP) and Duolink in situ proximity ligation assay (PLA) were performed to measure the interaction between Fascin and AKT2. Using in vitro and in vivo kinase assays, we confirmed that AKT2, but not AKT1 or AKT3, is an upstream kinase of Fascin Threonine 403. Taken together, the AKT2-catalyzed phosphorylation of Fascin Threonine 403 suppressed esophageal cancer cell behavior, actin-bundling activity, and filopodia formation.

Identifiants

DOI: 10.1016/j.biocel.2022.106188 PMID: 35219877
pubmed: 35219877
pii: S1357-2725(22)00033-4
doi: 10.1016/j.biocel.2022.106188
pii:
doi:

Substances chimiques

Actins 0
Carrier Proteins 0
Microfilament Proteins 0
fascin 146808-54-0
Threonine 2ZD004190S
Serine 452VLY9402
AKT2 protein, human EC 2.7.11.1
Proto-Oncogene Proteins c-akt EC 2.7.11.1

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

106188

Informations de copyright

Copyright © 2022 Elsevier Ltd. All rights reserved.

Auteurs

Zhi-Da Zhang (ZD)

The Key Laboratory of Molecular Biology for High Cancer Incidence Coastal Chaoshan Area, Department of Biochemistry and Molecular Biology, Shantou University Medical College, Shantou 515041, Guangdong, China. Electronic address: 19zdzhang@stu.edu.cn.

Bing Wen (B)

The Key Laboratory of Molecular Biology for High Cancer Incidence Coastal Chaoshan Area, Department of Biochemistry and Molecular Biology, Shantou University Medical College, Shantou 515041, Guangdong, China. Electronic address: 16bwen@stu.edu.cn.

Da-Jia Li (DJ)

The Key Laboratory of Molecular Biology for High Cancer Incidence Coastal Chaoshan Area, Department of Biochemistry and Molecular Biology, Shantou University Medical College, Shantou 515041, Guangdong, China. Electronic address: 18djli@stu.edu.cn.

Dan-Xia Deng (DX)

The Key Laboratory of Molecular Biology for High Cancer Incidence Coastal Chaoshan Area, Department of Biochemistry and Molecular Biology, Shantou University Medical College, Shantou 515041, Guangdong, China; Guangdong Provincial Key Laboratory of Infectious Diseases and Molecular Immunopathology, Institute of Oncologic Pathology, Shantou University Medical College, Shantou 515041, Guangdong, China. Electronic address: 19dxdeng@stu.edu.cn.

Xiao-Dong Wu (XD)

The Key Laboratory of Molecular Biology for High Cancer Incidence Coastal Chaoshan Area, Department of Biochemistry and Molecular Biology, Shantou University Medical College, Shantou 515041, Guangdong, China; Institute of Basic Medical Science, Medical Bioinformatics Center, Shantou University Medical College, Shantou 515041, Guangdong, China. Electronic address: 18xdwu@stu.edu.cn.

Yin-Wei Cheng (YW)

The Key Laboratory of Molecular Biology for High Cancer Incidence Coastal Chaoshan Area, Department of Biochemistry and Molecular Biology, Shantou University Medical College, Shantou 515041, Guangdong, China; Guangdong Provincial Key Laboratory of Infectious Diseases and Molecular Immunopathology, Institute of Oncologic Pathology, Shantou University Medical College, Shantou 515041, Guangdong, China; Institute of Basic Medical Science, Cancer Research Center, Shantou University Medical College, Shantou 515041, Guangdong, China. Electronic address: ywcheng@stu.edu.cn.

Lian-Di Liao (LD)

The Key Laboratory of Molecular Biology for High Cancer Incidence Coastal Chaoshan Area, Department of Biochemistry and Molecular Biology, Shantou University Medical College, Shantou 515041, Guangdong, China; Guangdong Provincial Key Laboratory of Infectious Diseases and Molecular Immunopathology, Institute of Oncologic Pathology, Shantou University Medical College, Shantou 515041, Guangdong, China. Electronic address: ldliao@stu.edu.cn.

Lin Long (L)

The Key Laboratory of Molecular Biology for High Cancer Incidence Coastal Chaoshan Area, Department of Biochemistry and Molecular Biology, Shantou University Medical College, Shantou 515041, Guangdong, China; Guangdong Provincial Key Laboratory of Infectious Diseases and Molecular Immunopathology, Institute of Oncologic Pathology, Shantou University Medical College, Shantou 515041, Guangdong, China; Institute of Basic Medical Science, Cancer Research Center, Shantou University Medical College, Shantou 515041, Guangdong, China. Electronic address: llong@stu.edu.cn.

Geng Dong (G)

The Key Laboratory of Molecular Biology for High Cancer Incidence Coastal Chaoshan Area, Department of Biochemistry and Molecular Biology, Shantou University Medical College, Shantou 515041, Guangdong, China; Institute of Basic Medical Science, Medical Bioinformatics Center, Shantou University Medical College, Shantou 515041, Guangdong, China. Electronic address: gdong@stu.edu.cn.

Li-Yan Xu (LY)

The Key Laboratory of Molecular Biology for High Cancer Incidence Coastal Chaoshan Area, Department of Biochemistry and Molecular Biology, Shantou University Medical College, Shantou 515041, Guangdong, China; Guangdong Provincial Key Laboratory of Infectious Diseases and Molecular Immunopathology, Institute of Oncologic Pathology, Shantou University Medical College, Shantou 515041, Guangdong, China; Institute of Basic Medical Science, Cancer Research Center, Shantou University Medical College, Shantou 515041, Guangdong, China. Electronic address: lyxu@stu.edu.cn.

En-Min Li (EM)

The Key Laboratory of Molecular Biology for High Cancer Incidence Coastal Chaoshan Area, Department of Biochemistry and Molecular Biology, Shantou University Medical College, Shantou 515041, Guangdong, China. Electronic address: nmli@stu.edu.cn.

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Classifications MeSH

questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines du cytosquelette › Protéines des microfilaments › Actines › AKT serine/threonine kinase 2-mediated...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines de transport › AKT serine/threonine kinase 2-mediated...
questionsmedicales.fr › Cellules › Cellules cultivées › Cellules cancéreuses en culture › Lignée cellulaire tumorale › AKT serine/threonine kinase 2-mediated...
questionsmedicales.fr › Maladies de l'appareil digestif › Maladies gastro-intestinales › Tumeurs gastro-intestinales › Tumeurs de l'oesophage › AKT serine/threonine kinase 2-mediated...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › AKT serine/threonine kinase 2-mediated...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines du cytosquelette › Protéines des microfilaments › AKT serine/threonine kinase 2-mediated...
questionsmedicales.fr › Métabolisme › Phosphorylation › AKT serine/threonine kinase 2-mediated...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines tumorales › Protéines oncogènes › Protéines proto-oncogènes › Protéines proto-oncogènes c-akt › AKT serine/threonine kinase 2-mediated...
questionsmedicales.fr › Acides aminés, peptides et protéines › Acides aminés › Acides aminés neutres › Sérine › AKT serine/threonine kinase 2-mediated...
questionsmedicales.fr › Acides aminés, peptides et protéines › Acides aminés › Acides aminés neutres › Thréonine › AKT serine/threonine kinase 2-mediated...