The DOI matches its Crossref record; 15 of the 15 references it cites were found in a registry or an index.
A Homeobox Protein, Prox1, Is Involved in the Differentiation, Proliferation, and Prognosis in Hepatocellular Carcinoma
Open accessAbstract
Purpose: It has been shown that a lymphatic differentiation master gene, prox1, also plays an essential role in fetal hepatocyte migration. Its expression is detected in embryonic hepatoblasts and in adult hepatocytes. Hepatoma cells are similar to embryonic hepatoblasts to a certain extent because they both proliferate and invade the surrounding tissue. To address the possibility that Prox1 may be involved in the tumorigenesis of hepatocellular carcinoma (HCC), human clinical samples were analyzed. Experimental Design: To screen prox1 as a potential tumor suppressor gene, its expression was analyzed in HCC cell lines and in human HCC tissues. Its growth-conferring abilities were assessed by transiently overexpressing Prox1 in HCC cell lines and by knocking down its expression by RNA interference. Results: We found that there was a significant correlation between Prox1 expression and the differentiation scores of the tumors. Subsequently, we also showed that low expression of Prox1 in tumors was closely associated with a poor prognosis. The specific knockdown of Prox1 by RNA interference strongly accelerated in vitro cell growth, whereas the overexpression of Prox1 greatly suppressed the growth. Conclusions: Our results suggest that Prox1 is involved in the differentiation and progression of HCC, and thus it may be a candidate for the development of novel diagnostic and therapeutic strategies for HCC.
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“but both tumor-promoting and suppressor roles have been reported in liver cancer models22,23”
From Active repression of cell fate plasticity by PROX1 safeguards hepatocyte identity and prevents liver tumorigenesis (2025) · cites this paper as [23]
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Prox1 Function Is Required for the Development of the Murine Lymphatic System
Wigle, J. T., & Oliver, G. C. (1999) · Cell · doi:10.1016/s0092-8674(00)81511-1 · Cited by 1,581
Epidemiology of Primary Liver Cancer
Bosch, F. X., Ribes, J., & Borràs, J. (1999) · Seminars in Liver Disease · doi:10.1055/s-2007-1007117 · Cited by 958 · cited 1×
“Other risk factors include prolonged dietary exposure to aflatoxin (2), primary hemochromatosis, and cirrhosis associated with genetic liver diseases (3); however, the principal risk factor varies among countries.”
BackgroundClassification and prediction of survival in hepatocellular carcinoma by gene expression profiling
Lee, J., Chu, I., Heo, J., Calvisi, D. F., Sun, Z., Roskams, T., Durnez, A., Demetris, A. J., & Thorgeirsson, S. S. (2004) · Hepatology · doi:10.1002/hep.20375 · Cited by 942
The prospero gene specifies cell fates in the drosophila central nervous system
Doe, C. Q., Chu‐LaGraff, Q., Wright, D. M., & Scott, M. P. (1991) · Cell · doi:10.1016/0092-8674(91)90463-9 · Cited by 454
Prox1 function is crucial for mouse lens-fibre elongation
Wigle, J. T., Chowdhury, K., Gruß, P., & Oliver, G. C. (1999) · Nature Genetics · doi:10.1038/6844 · Cited by 432
Dyer, M. A., Livesey, F. J., Cepko, C. L., & Oliver, G. C. (2003) · Nature Genetics · doi:10.1038/ng1144 · Cited by 406
Hepatocyte migration during liver development requires Prox1
Sosa-Pineda, B., Wigle, J. T., & Oliver, G. (2000) · Nature Genetics · doi:10.1038/76996 · Cited by 381
Prox 1, a prospero-related homeobox gene expressed during mouse development
Oliver, G. C., Sosa‐Pineda, B., Geisendorf, S., Spana, E. P., Doe, C. Q., & Gruß, P. (1993) · Mechanisms of Development · doi:10.1016/0925-4773(93)90012-m · Cited by 369
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Epidemiology of Hepatocellular Carcinoma
El‐Serag, H. B. (2001) · Clinics in Liver Disease · doi:10.1016/s1089-3261(05)70155-0 · Cited by 329
Prox1, master regulator of the lymphatic vasculature phenotype
Hong, Y., & Detmar, M. J. (2003) · Cell and Tissue Research · doi:10.1007/s00441-003-0747-8 · Cited by 133 · cited 1×
“gene prox1 is related to the Drosophila prospero gene, which mediates cell fate decisions of neuroblasts (5).”
BackgroundOkabe, H., Ikai, I., Matsuo, K., et al. (2000) · Hepatology · doi:10.1053/he.2000.6409 · Cited by 96
Self-citationMutations and aberrant DNA methylation of the PROX1 gene in hematologic malignancies
Nagai, H., Li, Y., Hatano, S., Ohno, T., Yuge, M., Ito, E., Utsumi, M., Saito, H., & Kinoshita, T. (2003) · Genes Chromosomes and Cancer · doi:10.1002/gcc.10248 · Cited by 60
Dudás, J., Papoutsi, M., Hecht, M., Elmaouhoub, A., Saile, B., Christ, B., Tomarev, S. I., von Kaisenberg, C. S., Schweigerer, L., Ramadori, G. P., et al. (2004) · Anatomy and Embryology · doi:10.1007/s00429-004-0403-4 · Cited by 53
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Nuclear Receptor Coregulators and Human Disease
Lonard, D. M., Lanz, R. B., & O’Malley, B. W. (2007) · Endocrine Reviews · doi:10.1210/er.2007-0012 · Cited by 318
Petrova, T. V., Nykänen, A. I., Norrmén, C., Ivanov, K. I., Andersson, L. C., Haglund, C. H., Puolakkainen, P. A., Wempe, F., von Melchner, H., Gradwohl, G., et al. (2008) · Cancer Cell · doi:10.1016/j.ccr.2008.02.020 · Cited by 194
Role of epigenetic aberrations in the development and progression of human hepatocellular carcinoma
Pogribny, I. P., & Rusyn, I. (2012) · Cancer Letters · doi:10.1016/j.canlet.2012.01.038 · Cited by 174
“Among genes frequently methylated in HCC are tumor suppressors, including RASSF1A [56], p16INK4A [57,58], p15INK4B [59], RB1 [60], SOCS1 [61,62], SOCS3 [63], SYC [64], GSTP1 [65], NQO1 [66], PROX1 [67,68], NORE1B [69], RIZ1 [70], RELN [71], FBLN1 [72], and PAX5 [73].”
Transcription factor PROX1: its role in development and cancer
Elsir, T., Smits, A., Lindström, M. S., & Nistér, M. (2012) · Cancer and Metastasis Reviews · doi:10.1007/s10555-012-9390-8 · Cited by 158
“In contrast to its putative oncogenic role in colorectal cancer, depletion of PROX1 in human hepatocellular carcinoma cell lines by siRNA caused a significant increase in cell proliferation, while over-expression decreased cell proliferation by 30 % and more [68].”
BackgroundInfluentialThe Hepatic Lymphatic Vascular System: Structure, Function, Markers, and Lymphangiogenesis
Tanaka, M., & Iwakiri, Y. (2016) · Cellular and Molecular Gastroenterology and Hepatology · doi:10.1016/j.jcmgh.2016.09.002 · Cited by 146
Metadata
- Authors
- Shimoda, M., Takahashi, M., Yoshimoto, T., Kono, T., Ikai, I., & Kubo, H.
- Affiliations
- Kyoto University (JP)
- 1Molecular and Cancer Research Unit, HMRO, and
- Venue
- Clinical Cancer Research
- Published
- 2006-10-15
- Volume
- 12
- Issue
- 20
- Pages
- 6005-6011
- ISSN
- 1078-0432 (ISSN-L)
- 1557-3265
- OpenAlex
- W2133384911
- Semantic Scholar
- 36f5c5b98748041985bc89acca6189a59ec35025
- Cited by
- 106
- References
- 15
- Citations by year
- 2025: 5 · 2024: 5 · 2023: 2 · 2022: 5 · 2021: 1 · 2020: 3 · 2019: 6 · 2018: 4 · 2017: 3 · 2016: 4 · 2015: 7 · 2014: 5 · 2013: 5 · 2012: 12
- FWCI
- 5.45
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by
- Locations
- Clinical Cancer Research (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Kyoto University Research Information Repository (Kyoto University) (submittedVersion)
- Funders
- Ichiro Kanehara Foundation for the Promotion of Medical Sciences and Medical Care
- Princess Takamatsu Cancer Research Fund
- Topics
- Health Sciences › Medicine › Hepatology › Hepatocellular Carcinoma Treatment and Prognosis
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer-related molecular mechanisms research
- Keywords
- Prox1, homeodomain transcription factor, hepatocellular carcinoma, tumor suppressor, hepatocyte differentiation, tumor cell proliferation, prognosis, hepatoblasts, RNAi knockdown, gene overexpression
- MeSH terms
- Prospero-Related Homeobox 1 Protein, Cell Differentiation, Cell Division, Female, Carcinoma, Hepatocellular, Humans, Liver Neoplasms, Lymphatic Metastasis, Male, Neoplasm Metastasis, Prognosis, RNA, Neoplasm, Gene Expression Regulation, Neoplastic, Genes, Tumor Suppressor, DNA Primers, Homeodomain Proteins, Reverse Transcriptase Polymerase Chain Reaction, Tumor Suppressor Proteins, RNA Interference
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