Lasp1 interacts with n-wasp to activate the arp2/3 complex and facilitate colorectal cancer metastasis by increasing tumour budding and worsening the pattern of invasion

ABSTRACT LIM and SH3 protein 1 (LASP1) is a metastasis-related protein reported to enhance tumour progression in colorectal cancer (CRC). However, the underlying mechanism is still elusive.

As the major biological and pathological functions of LASP1 are accomplished by its LIM and SH3 domains via protein–protein interactions, a yeast two-hybrid system was employed to screen

novel LASP1-interacting proteins. N-WASP, a member of the Wiskott–Aldrich syndrome protein (WASP) family, was screened and identified as a LASP1-interacting protein overexpressed in CRC

tissues. N-WASP could stimulate the migration and invasion of CRC cells in vitro and increase the formation of subcutaneous tumours, mesenteric implanted tumours and hepatic metastatic

tumours. N-WASP could interact with and activate the Arp2/3 complex to stimulate actin polymerization, thus changing the migratory and invasive capabilities of CRC cells. The interaction of

LASP1 with N-WASP did not influence the expression of N-WASP but recovered the reduced actin polymerization induced by N-WASP silencing. High N-WASP expression was detected in most clinical

colorectal samples, and it was positively correlated with the expression of LASP1 and ARP3, as well as the tumour budding and pattern of invasion, but negatively correlated with host

lymphocytic response. Our study suggests a new mechanism for LASP1-mediated CRC metastasis determined by exploring LASP1-interacting proteins and identifies N-WASP as a potential therapeutic

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Contact customer support SIMILAR CONTENT BEING VIEWED BY OTHERS RIPK2 PROMOTES COLORECTAL CANCER METASTASIS BY PROTECTING YAP DEGRADATION FROM ITCH-MEDIATED UBIQUITINATION Article Open

access 04 April 2025 ABLIM1, A NOVEL UBIQUITIN E3 LIGASE, PROMOTES GROWTH AND METASTASIS OF COLORECTAL CANCER THROUGH TARGETING IĸBΑ UBIQUITINATION AND ACTIVATING NF-ĸB SIGNALING Article

Open access 16 January 2024 CCT8 RECOVERS WTP53-SUPPRESSED CELL CYCLE EVOLUTION AND EMT TO PROMOTE COLORECTAL CANCER PROGRESSION Article Open access 03 December 2021 REFERENCES * Cronin KA,

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National Natural Science Foundation of China (Nos. 81773082, 81702903, 81872423, 81972813), Guangdong Natural Science Foundation (2018B030311036, 2019A1515010974) and Fork Ying Tung

Education Foundation (161035). AUTHOR INFORMATION Author notes * These authors contributed equally: Pingping Yan, Jian Liu, Rui Zhou AUTHORS AND AFFILIATIONS * Department of Pathology,

Nanfang Hospital, Southern Medical University, Guangzhou, China Pingping Yan, Jian Liu, Rui Zhou, Chuang Lin, Lijun Xu & Liang Zhao * Department of Pathology, School of Basic Medical

Sciences, Southern Medical University, Guangzhou, China Pingping Yan, Jian Liu, Rui Zhou, Lijun Xu & Liang Zhao * Guangdong Province Key Laboratory of Molecular Tumor Pathology, Southern

Medical University, Guangzhou, China Pingping Yan, Jian Liu, Rui Zhou, Lijun Xu & Liang Zhao * Department of Pathology, Guangdong Women and Children Hospital, 511442, Guangdong, China

Kunhe Wu * Gastrointestinal Surgical Center, The First Affiliated Hospital of Sun Yat-Sen University, 510080, Guangzhou, China Shibin Yang * Department of Neurosurgery, The First Affiliated

Hospital of Sun Yat-Sen University, 510080, Guangzhou, China Shuai Yang * Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Southern Medical University,

510515, Guangzhou, China Jueyu Zhou * Department of Medical Oncology, Affiliated Tumor Hospital of Guangzhou Medical University, Guangzhou, China Hui Wang Authors * Pingping Yan View author

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Shuai Yang View author publications You can also search for this author inPubMed Google Scholar * Jueyu Zhou View author publications You can also search for this author inPubMed Google

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Google Scholar * Liang Zhao View author publications You can also search for this author inPubMed Google Scholar CONTRIBUTIONS LZ led study design and prepared the paper; P-PY, JL and RZ

carried out the experiments; CL, S-BY, and SY assisted in tissue sample collection and clinical analysis; K-HW and J-YZ performed statistical analysis; L-JX, and HW performed data analysis

and interpretation. CORRESPONDING AUTHOR Correspondence to Liang Zhao. ETHICS DECLARATIONS CONFLICT OF INTEREST The authors declare that they have no conflict of interest. ADDITIONAL

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INFORMATION RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Yan, P., Liu, J., Zhou, R. _et al._ LASP1 interacts with N-WASP to activate the Arp2/3

complex and facilitate colorectal cancer metastasis by increasing tumour budding and worsening the pattern of invasion. _Oncogene_ 39, 5743–5755 (2020).

https://doi.org/10.1038/s41388-020-01397-7 Download citation * Received: 28 April 2020 * Accepted: 16 July 2020 * Published: 23 July 2020 * Issue Date: 27 August 2020 * DOI:

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