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High expression of small GTPase Rab3D promotes cancer progression and metastasis
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// Jian Yang 1,2,3 , Wei Liu 1,2,3 , Xin’an Lu 1,2,3 , Yan Fu 1,2,3 , Lin Li 1,2,3 and Yongzhang Luo 1,2,3 1 National Engineering Laboratory for Anti-tumor Protein Therapeutics, Tsinghua University, Beijing, China 2 Beijing Key Laboratory for Protein Therapeutics, Tsinghua University, Beijing, China 3 Cancer Biology Laboratory, School of Life Sciences, Tsinghua University, Beijing, China Correspondence to: Yongzhang Luo, email: // Keywords : Rab3D, EMT, exosomes, Hsp90α, tumor metastasis Received : February 02, 2015 Accepted : February 21, 2015 Published : March 14, 2015 Abstract Rab GTPases control exocytic and endocytic membrane trafficking such as exosomes release. As a secretory small GTPase, Rab3D is a vital regulator for protein secretion. However, the role of Rab3D in cancer was never systematically studied. The aim of this study is to examine its function and mechanism in cancer, especially metastasis. We detected protein levels of Rab3D in nine cancer cell lines and twelve types of clinical cancer specimens. Subsequently, we established in vitro migration and in vivo orthotopic metastatic mouse models to study the role of Rab3D in tumor metastasis. Here, we reported that the expression levels of Rab3D were dysregulated in cancer cells and highly correlated with tumor malignancies in the clinical samples. Increased expressions of Rab3D led to tumor invasion in vitro and lung metastasis in vivo , whereas Rab3D knockdown suppressed the tumor cell motility. Mechanistic studies revealed that Rab3D activated intracellular the AKT/GSK3β signaling to induce the EMT process. In addition, it also regulated the extracellular secretion of Hsp90α to promote tumor cell migration and invasion. These results prove that Rab3D is a key molecule to regulate tumor metastasis, suggesting that blocking the Rab3D function can be a potential therapeutic approach for cancer metastasis.
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RAB3D induces breast cancer cell invasion by activating Akt/GSK-3β/Snail pathway.
“Elevated expression of RAB3C promotes in vivo migration, invasion, and metastasis of colorectal cancer while RAB3D induced breast cancer cell invasion by activating Akt/GSK-3β/Snail pathway [115,116].”
From Insights of Endocytosis Signaling in Health and Disease (2023) · cites this paper as [116]
Elevated expression of RAB3C promotes in vivo migration, invasion, and metastasis of colorectal cancer.
“Elevated expression of RAB3C promotes in vivo migration, invasion, and metastasis of colorectal cancer while RAB3D induced breast cancer cell invasion by activating Akt/GSK-3β/Snail pathway [115,116].”
From Insights of Endocytosis Signaling in Health and Disease (2023) · cites this paper as [116]
The Results sections on cell motility and in vivo metastasis study Rab3D in breast-cancer cell models, not Rab3C in colorectal cancer. A search for Rab3C and colorectal cancer found no passage supporting the quoted claim. The paper does support the citing sentence’s separate Rab3D clause. (LLM, conf=0.78)
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Insights of Endocytosis Signaling in Health and Disease
Pathak, C., Vaidya, F. U., Waghela, B. N., Jaiswara, P. K., Gupta, V. K., Kumar, A., Rajendran, B. K., & Ranjan, K. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24032971 · Cited by 59
Metadata
- Authors
- Yang, J., Liu, W., Lu, X., Fu, Y., Li, L., & Luo, Y.
- Affiliations
- Tsinghua University (CN)
- Venue
- Oncotarget
- Publisher
- Impact Journals, LLC
- Published
- 2015-03-14
- Volume
- 6
- Issue
- 13
- Pages
- 11125-11138
- ISSN
- 1949-2553 (ISSN-L)
- PMC
- PMC4484444
- OpenAlex
- W1741277085
- Cited by
- 107
- References
- 5
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 3 · 2023: 10 · 2022: 12 · 2021: 10 · 2020: 33 · 2019: 7 · 2018: 10 · 2017: 12 · 2016: 5 · 2015: 1
- FWCI
- 4.98
- Type
- journal article
- Language
- en
- Open access
- diamond
- doi.org
- Licence
- cc-by
- Locations
- Oncotarget (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China (81272529, 81171998, 81472667, 81461148021)
- National Science and Technology Major Project
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Extracellular vesicles in disease
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mechanisms of cancer metastasis
- Keywords
- Rab3D, small GTPases, metastasis, epithelial-mesenchymal transition, exosomes, Akt/GSK-3β signaling, tumor cell migration, tumor invasion, lung metastasis, tumor progression
- MeSH terms
- Animals, Breast Neoplasms, Cell Movement, Female, Fluorescent Antibody Technique, Humans, Immunoenzyme Techniques, Lung Neoplasms, Neoplasm Staging, Neoplasms, Prognosis, Tumor Cells, Cultured, Blotting, Western, Apoptosis, rab3 GTP-Binding Proteins, Xenograft Model Antitumor Assays, RNA, Small Interfering, Tissue Array Analysis, Cell Proliferation, Mice
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