Cited by 257Protein Kinase Regulation and GTPase SignalingCell Adhesion Molecules ResearchMechanisms of cancer metastasis

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Roles of Rap1 signaling in tumor cell migration and invasion

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Yi-Lei, Zhang, Yi-Lei, Zhang, Ruo-Chen, Wang, Ken, Cheng, Brian Z., Ring, Li, Su, Ruo-Chen, Wang, Ken, Cheng, Brian Z., Ring, Li, Su·2017·Cancer Biology & Medicine

DOI 10.20892/j.issn.2095-3941.2016.0086PMC PMC5365179

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Abstract

Ras-associated protein-1 (Rap1), a small GTPase in the Ras-related protein family, is an important regulator of basic cellular functions (e.g., formation and control of cell adhesions and junctions), cellular migration, and polarization. Through its interaction with other proteins, Rap1 plays many roles during cell invasion and metastasis in different cancers. The basic function of Rap1 is straightforward; it acts as a switch during cellular signaling transduction and regulated by its binding to either guanosine triphosphate (GTP) or guanosine diphosphate (GDP). However, its remarkably diverse function is rendered by its interplay with a large number of distinct Rap guanine nucleotide exchange factors and Rap GTPase activating proteins. This review summarizes the mechanisms by which Rap1 signaling can regulate cell invasion and metastasis, focusing on its roles in integrin and cadherin regulation, Rho GTPase control, and matrix metalloproteinase expression.

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1 Mechanisms by which Rap1 signaling controls tumor cell invasion and metastasis. Rap1 signaling regulates integrin- or cadherin-mediated cell adhesion, expression levels of proteases (e.g., matrix metalloproteinase), and cytoskeletal changes, which are linked to tumor cell proliferation, invasion, and metastasis.CC BY-NC-SA · PubMed Central

2 Dynamic change in Rap1 signaling during tumor cell invasion and metastasis. Dynamic change or cycling of Rap1 activity is required for invasive and metastatic behavior of tumor cells. For instance, while inactivation of Rap1-cadherin or integrin signaling is associated with reduced cell‒cell adhesion or cell adhesion to extracellular matrix in one stage (steps 1 and 3), a separate step might entail increased Rap1 activity and cell adhesion (steps 2, 4, 5, and 6).CC BY-NC-SA · PubMed Central

3 Subcellular localization of Rap1 and SIPA1 during tumor cell invasion and metastasis.CC BY-NC-SA · PubMed Central

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Authors: Yi-Lei, Z., Yi-Lei, Z., Ruo-Chen, W., Ken, C., Brian Z., R., Li, S., Ruo-Chen, W., Ken, C., Brian Z., R., & Li, S.
Venue: Cancer Biology & Medicine
Publisher: China Anti-cancer Association
Published: 2017
Volume: 14
Issue: 1
Pages: 90-99
ISSN: 2095-3941 (ISSN-L)
DOI: 10.20892/j.issn.2095-3941.2016.0086
PMC: PMC5365179
OpenAlex: W2592760610
Cited by: 244
References: 80
Citations by year: 2026: 23 · 2025: 35 · 2024: 32 · 2023: 24 · 2022: 33 · 2021: 23 · 2020: 28 · 2019: 23 · 2018: 22 · 2017: 1
FWCI: 8.27
Type: journal article
Language: en
Open access: gold
doi.org
Licence: cc-by
Locations: Cancer Biology and Medicine (publishedVersion, cc-by)
Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-sa)
PubMed Central (publishedVersion, cc-by-nc-sa)
PubMed (publishedVersion)
DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders: National Natural Science Foundation of China
Shenzhen Municipal Science and Technology Innovation Council
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
Health Sciences › Medicine › Immunology and Allergy › Cell Adhesion Molecules Research
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mechanisms of cancer metastasis
Keywords: Rap1, tumor cell migration, tumor invasion, metastasis, guanine nucleotide exchange factor, GTPase-activating protein, integrin regulation, Rho GTPases, matrix metalloproteinase expression, cell adhesion, cell polarity

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Roles of Rap1 signaling in tumor cell migration and invasion

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