The DOI matches its Crossref record; 75 of the 75 references it cites were found in a registry or an index.
Cooperative interactions of PTEN deficiency and RAS activation in melanoma metastasis
Open accessAbstract
Mitogen-activated protein kinase (MAPK) and AKT pathways are frequently co-activated in melanoma through overexpression of receptor tyrosine kinases, mutations in their signaling surrogates, such as RAS and BRAF, or loss of negative regulators such as PTEN. As RAS can be a positive upstream regulator of PI3-K, it has been proposed that the loss of PTEN and the activation of RAS are redundant events in melanoma pathogenesis. Here, in genetically engineered mouse models of cutaneous melanomas, we sought to better understand the genetic interactions between HRAS activation and PTEN inactivation in melanoma genesis and progression in vivo. We showed that HRAS activation cooperates with Pten+/- and Ink4a/Arf-/- to increase melanoma penetrance and promote metastasis. Correspondingly, gain- and loss-of-function studies established that Pten loss increases invasion and migration of melanoma cells and non-transformed melanocytes, and such biological activity correlates with a shift to phosphorylation of AKT2 isoform and E-cadherin down-regulation. Thus, Pten inactivation can drive the genesis and promote the metastatic progression of RAS activated Ink4a/Arf deficient melanomas.
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“Various levels of interplay are known between the PI3K-AKT and KRAS-MAPK signaling cascades139, including for potential therapy.”
From The metabolic landscape of RAS-driven cancers from biology to therapy (2021) · cites this paper as [139]
In the citing paper
“Network analysis of the several driver mutation genes, including KMT2D138, PIK3CA139, PTEN140, and IDH1141, that regulate signaling and metabolic pathways in KRAS-driven cancers, connects them to oncogenic RAS (Fig 4c).”
From The metabolic landscape of RAS-driven cancers from biology to therapy (2021) · cites this paper as [139]
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1 retracted
AKT2 Inhibition of Cisplatin-induced JNK/p38 and Bax Activation by Phosphorylation of ASK1
Yuan, Z., Feldman, R. I., Sussman, G. E., Coppola, D., Nicosia, S. V., & Cheng, J. Q. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m302674200 · Cited by 202
RetractedMutations of the BRAF gene in human cancer
Davies, H., Bignell, G. R., Cox, C., Stephens, P., Edkins, S., Clegg, S., Teague, J., Woffendin, H., Garnett, M. J., Bottomley, W., et al. (2002) · Nature · doi:10.1038/nature00766 · Cited by 10,674
Li, J., Yen, C., Liaw, D., Podsypanina, K., Bose, S., Wang, S. I., Puc, J., Miliaresis, C., Rodgers, L., McCombie, R., et al. (1997) · Science · doi:10.1126/science.275.5308.1943 · Cited by 4,785
A System for Stable Expression of Short Interfering RNAs in Mammalian Cells
Brummelkamp, T. R., Bernards, R., & Agami, R. (2002) · Science · doi:10.1126/science.1068999 · Cited by 4,295
Steck, P. A., Pershouse, M. A., Jasser, S. A., Yung, W. K. A., Lin, H., Ligon, A. H., Langford, L. A., Baumgard, M. L., Hattier, T., Davis, T., et al. (1997) · Nature Genetics · doi:10.1038/ng0497-356 · Cited by 2,742
High frequency of BRAF mutations in nevi
Pollock, P. M., Harper, U. L., Hansen, K. S., Yudt, L. M., Stark, M., Robbins, C. M., Moses, T. Y., Hostetter, G., Wagner, U., Kakareka, J., et al. (2003) · Nature Genetics · doi:10.1038/ng1054 · Cited by 1,730
Role of the INK4a Locus in Tumor Suppression and Cell Mortality
Serrano, M., Lee, H.-W., Chin, L., Cordon-Cardo, C., Beach, D., & DePinho, R. A. (1996) · Cell · doi:10.1016/s0092-8674(00)81079-x · Cited by 1,585
Self-citationPten is essential for embryonic development and tumour suppression
Cristofano, A. D., Pesce, B., Cordon‐Cardo, C., & Pandolfi, P. P. (1998) · Nature Genetics · doi:10.1038/1235 · Cited by 1,518
Beyond PTEN mutations: the PI3K pathway as an integrator of multiple inputs during tumorigenesis
Cully, M., You, H., Levine, A. J., & Mak, T. W. (2006) · Nature reviews. Cancer · doi:10.1038/nrc1819 · Cited by 1,267
BrafV600E cooperates with Pten loss to induce metastatic melanoma
Dankort, D., Curley, D. P., Cartlidge, R. A., Nelson, B., Karnezis, A. N., Damsky Jr, W. E., You, M. J., DePinho, R. A., McMahon, M., & Bosenberg, M. (2009) · Nature Genetics · doi:10.1038/ng.356 · Cited by 1,189
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Items 101–108 of 108
Yokoyama, S., Yasuta, Y., Nagai, S., Mouri, S., Kaminaka, R., Ishida, K., Tanaka, A., Zhou, Y., & Sakurai, H. (2023) · Research Square · doi:10.21203/rs.3.rs-2572171/v1
New Therapeutic Approaches in Signaling
Flaherty, K. T. (2011) · Springer eBooks · doi:10.1007/978-3-7091-0371-5_16
Epigenetic dysregulation of novel candidate genes in melanoma
Wang, H. (2013) · Discovery Research Portal (University of Dundee)
Rôle et modes d'action de la Tétraspanine 8 dans l'invasion précoce du mélanome cutané
Kharbili, M. E. (2013) · theses.fr (ABES) · doi:10.70675/3e596898z95f7z4eb2za2aaz44ee31529d70
Tisserand, J. C. (2016) · theses.fr (ABES) · doi:10.70675/75c7849fz8b54z4676zbd10z2a0e877439d8
Wei, S. (2026) · Journal of Clinical and Translational Pathology · doi:10.14218/jctp.2026.00045
Metadata
- Authors
- Nogueira, C., Kim, K.-H., Sung, H., Paraiso, K. H. T., Dannenberg, J.-H., Bosenberg, M., Chin, L., & Kim, M.
- Affiliations
- Dana-Farber Cancer Institute (US)
- Moffitt Cancer Center (US)
- University of Vermont (US)
- Harvard University (US)
- Corresponding author
- Chin, L
- Kim, M
- Venue
- Oncogene
- Published
- 2010-08-16
- Volume
- 29
- Issue
- 47
- Pages
- 6222-6232
- ISSN
- 0950-9232 (ISSN-L)
- 1476-5594
- PMC
- PMC2989338
- OpenAlex
- W2147690515
- Cited by
- 108
- References
- 75
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 3 · 2023: 4 · 2022: 6 · 2021: 10 · 2020: 2 · 2019: 3 · 2018: 6 · 2017: 7 · 2016: 8 · 2015: 6 · 2014: 4 · 2013: 15 · 2012: 14
- FWCI
- 6.00
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Oncogene (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Cancer Institute (R01CA93947, R01CA093947, U01CA084313, UO1 CA84313)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Melanoma and MAPK Pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Tyrosine Phosphatases
- Keywords
- melanoma, PTEN loss, Ras activation, HRAS, CDKN2A, Ink4a/Arf, melanoma metastasis, genetic interactions, PI3K/Akt signaling, E-cadherin, epithelial-mesenchymal transition, tumor cell migration and invasion, Akt2 phosphorylation, RNA interference
- MeSH terms
- Animals, Cell Transformation, Neoplastic, Enzyme Activation, Humans, Isoenzymes, Melanocytes, Melanoma, Neoplasm Invasiveness, Neoplasm Metastasis, Down-Regulation, Cadherins, Proto-Oncogene Proteins p21(ras), Cell Line, Tumor, Proto-Oncogene Proteins c-akt, PTEN Phosphohydrolase, Mice, Gene Knockdown Techniques
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