Dynamic MAPK signaling activity underlies a transition from growth arrest to proliferation in Drosophila scribble mutant tumors
Open accessAbstract
Human tumors exhibit plasticity and evolving capacity over time. It is difficult to study the mechanisms of how tumors change over time in human patients, in particular during the early stages when a few oncogenic cells are barely detectable. Here, we used a Drosophila tumor model caused by loss of scribble (scrib), a highly conserved apicobasal cell polarity gene, to investigate the spatial-temporal dynamics of early tumorigenesis events. The fly scrib mutant tumors have been successfully used to model many aspects of tumorigenesis processes. However, it is still unknown whether Drosophila scrib mutant tumors exhibit plasticity and evolvability along the temporal axis. We found that scrib mutant tumors displayed different growth rates and cell cycle profiles over time, indicative of a growth arrest-to-proliferation transition as the scrib mutant tumors progress. Longitudinal bulk and single-cell transcriptomic analysis of scrib mutant tumors revealed that the MAPK pathway, including JNK and ERK signaling activities, showed quantitative changes over time. We found that high JNK signaling activity caused G2/M cell cycle arrest in early scrib mutant tumors. In addition, JNK signaling activity displayed a radial polarity with the JNKhigh cells located at the periphery of scrib mutant tumors, providing an inherent mechanism that leads to an overall decrease in JNK signaling activity over time. We also found that ERK signaling activity, in contrast to JNK activity, increased over time and promoted growth in late-stage scrib mutant tumors. Furthermore, high JNK signaling activity repressed ERK signaling activity in early scrib mutant tumors. Together, these data demonstrate that dynamic MAPK signaling activity, fueled by intratumor heterogeneity derived from tissue topological differences, drives a growth arrest-to-proliferation transition in scrib mutant tumors. This article has an associated First Person interview with the joint first authors of the paper.
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Previously ectopic upregulation of a network of transcription factors (Upd, JAK-STAT, AP-1, Myc, Ftz, Ets, Irbp18, Xrp1, Slow border, and Vrille) promotes growth and invasiveness of RasV12,scrib- tumours.
“Previously ectopic upregulation of a network of transcription factors e.g., Upd, JAK-STAT, AP-1, Myc, Ftz, Ets, Irbp18, Xrp1, Slow border, and Vrille were reported to promote the growth and invasiveness of the Ras V12 ,scrib -tumours (53-57).”
From A Tumour-Specific Molecular Network Promotes Tumour Growth in <i>Drosophila</i> by Enforcing a JNK-YKI Feedforward Loop (2023) · cites this paper as [57]
The Results section ('ERK signaling activity increases over time and promotes tumor growth'; page unavailable) reports that RasV12 overexpression increased the size of late-stage scrib mutant tumors. It does not show that ectopic upregulation of the listed transcription-factor network promotes growth or invasiveness; it also reports that RasV12 did not relieve early-tumor growth arrest. (LLM, conf=0.83)
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Cites
Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2
Love, M. I., Huber, W., & Anders, S. (2014) · Genome Biology · doi:10.1186/s13059-014-0550-8 · Cited by 95,106 · see citing works
STAR: ultrafast universal RNA-seq aligner
Dobin, A., Davis, C. A., Schlesinger, F., Drenkow, J., Zaleski, C., Jha, S., Batut, P., Chaisson, M., & Gingeras, T. R. (2013) · Bioinformatics · doi:10.1093/bioinformatics/bts635 · Cited by 51,709 · see citing works
Robinson, M. D., McCarthy, D. J., & Smyth, G. K. (2010) · Bioinformatics · doi:10.1093/bioinformatics/btp616 · Cited by 41,364 · see citing works
clusterProfiler: an R Package for Comparing Biological Themes Among Gene Clusters
Yu, G., Wang, L.-G., Han, Y., & He, Q.-Y. (2012) · OMICS: A Journal of Integrative Biology · doi:10.1089/omi.2011.0118 · Cited by 36,259 · see citing works
Integrating single-cell transcriptomic data across different conditions, technologies, and species
Butler, A., Hoffman, P., Smibert, P., Papalexi, E., & Satija, R. (2018) · Nature Biotechnology · doi:10.1038/nbt.4096 · Cited by 13,174 · see citing works
Intratumor Heterogeneity and Branched Evolution Revealed by Multiregion Sequencing
Gerlinger, M., Rowan, A. J., Horswell, S., Larkin, J., Endesfelder, D., Gronroos, E., Martinez, P., Matthews, N., Stewart, A., Tarpey, P., et al. (2012) · New England Journal of Medicine · doi:10.1056/nejmoa1113205 · Cited by 7,774 · cited 1× · see citing works
“For example, individual tumor cells can acquire different types of mutations and grow into distinct subclones within the same tumor (de Bruin et al., 2014; Gerlinger et al., 2012).”
The Subread aligner: fast, accurate and scalable read mapping by seed-and-vote
Liao, Y., Smyth, G. K., & Shi, W. (2013) · Nucleic Acids Research · doi:10.1093/nar/gkt214 · Cited by 3,064 · see citing works
Clonal heterogeneity and tumor evolution: past, present, and the future
McGranahan, N., & Swanton, C. (2017) · Cell · doi:10.1016/j.cell.2017.01.018 · Cited by 2,840 · see citing works
The Glial Nature of Embryonic and Adult Neural Stem Cells
Kriegstein, A., & Alvarez-Buylla, A. (2009) · Annual Review of Neuroscience · doi:10.1146/annurev.neuro.051508.135600 · Cited by 2,475 · see citing works
Spatial and temporal diversity in genomic instability processes defines lung cancer evolution
de Bruin, E. C., McGranahan, N., Mitter, R., Salm, M., Wedge, D. C., Yates, L., Jamal-Hanjani, M., Shafi, S., Murugaesu, N., Rowan, A. J., et al. (2014) · Science · doi:10.1126/science.1253462 · Cited by 1,117 · see citing works
Expression of baculovirus P35 prevents cell death in Drosophila
Hay, B. A., Wolff, T., & Rubin, G. M. (1994) · Development · doi:10.1242/dev.120.8.2121 · Cited by 1,066 · see citing works
Minutes: Mutants of Drosophila autonomously affecting cell division rate
Morata, G., & Ripoll, P. L. (1975) · Developmental Biology · doi:10.1016/0012-1606(75)90330-9 · Cited by 983 · see citing works
Cooperative Regulation of Cell Polarity and Growth by Drosophila Tumor Suppressors
Bilder, D. H., Li, M., & Perrimon, N. (2000) · Science · doi:10.1126/science.289.5476.113 · Cited by 916 · see citing works
Woods, D. F., & Bryant, P. J. (1991) · Cell · doi:10.1016/0092-8674(81)90009-x · Cited by 898 · see citing works
Martı́n-Blanco, E., Gampel, A., Ring, J., Virdee, K., Kirov, N., Tolkovsky, A. M., & Martínez-Arias, A. (1998) · Genes & Development · doi:10.1101/gad.12.4.557 · Cited by 673 · see citing works
scribble mutants cooperate with oncogenic Ras or Notch to cause neoplastic overgrowth in Drosophila
Brumby, A. M., & Richardson, H. E. (2003) · The EMBO Journal · doi:10.1093/emboj/cdg548 · Cited by 628 · see citing works
Bilder, D. H. (2004) · Genes & Development · doi:10.1101/gad.1211604 · Cited by 547 · see citing works
A Genetic Screen in <i>Drosophila</i> for Metastatic Behavior
Pagliarini, R. A., & Xu, T. (2003) · Science · doi:10.1126/science.1088474 · Cited by 543 · see citing works
Sprouty, an intracellular inhibitor of Ras signaling
Casci, T., Vinós, J., & Freeman, M. (1999) · Cell · doi:10.1016/s0092-8674(00)80576-0 · Cited by 467 · see citing works
Microenvironmental autophagy promotes tumour growth
Katheder, N. S., Khezri, R., O’Farrell, F., Schultz, S. W., Jain, A., Rahman, M. M., Schink, K. O., Theodossiou, T. A., Johansen, T., Juhász, G., et al. (2017) · Nature · doi:10.1038/nature20815 · Cited by 452 · see citing works
Jiménez-Sánchez, A., Memon, D., Pourpe, S., Veeraraghavan, H., Li, Y., Vargas, H. A., Gill, M. B., Park, K. J., Zivanovic, O., Konner, J. A., et al. (2017) · Cell · doi:10.1016/j.cell.2017.07.025 · Cited by 449 · see citing works
Rebay, I., Fehon, R. G., & Artavanis‐Tsakonas, S. (1993) · Cell · doi:10.1016/0092-8674(93)90423-n · Cited by 413 · see citing works
JNK‐ and Fos‐regulated Mmp1 expression cooperates with Ras to induce invasive tumors in Drosophila
Uhlirova, M., & Bohmann, D. (2006) · The EMBO Journal · doi:10.1038/sj.emboj.7601401 · Cited by 395 · see citing works
Loss of Cell Polarity Drives Tumor Growth and Invasion through JNK Activation in Drosophila
Igaki, T., Pagliarini, R. A., & Xu, T. (2006) · Current Biology · doi:10.1016/j.cub.2006.04.042 · Cited by 370 · see citing works
Vaccari, T., & Bilder, D. H. (2005) · Developmental Cell · doi:10.1016/j.devcel.2005.09.019 · Cited by 365 · see citing works
Karim, F. D., & Rubin, G. M. (1998) · Development · doi:10.1242/dev.125.1.1 · Cited by 302 · see citing works
Fly-FUCCI: A Versatile Tool for Studying Cell Proliferation in Complex Tissues
Zielke, N., Korzelius, J., van Straaten, M., Bender, K., Schuhknecht, G. F. P., Dutta, D., Xiang, J., & Edgar, B. A. (2014) · Cell Reports · doi:10.1016/j.celrep.2014.03.020 · Cited by 286 · see citing works
Drosophila melanogaster: a model and a tool to investigate malignancy and identify new therapeutics
González, C. (2013) · Nature reviews. Cancer · doi:10.1038/nrc3461 · Cited by 281 · see citing works
Topography of cancer-associated immune cells in human solid tumors
Kather, J. N., Suarez‐Carmona, M., Charoentong, P., Weis, C., Hirsch, D. D., Bankhead, P., Horning, M., Ferber, D., Kel, I., Herpel, E., et al. (2018) · eLife · doi:10.7554/elife.36967 · Cited by 277 · see citing works
Ras1 Promotes Cellular Growth in the Drosophila Wing
Prober, D. A., & Edgar, B. A. (2000) · Cell · doi:10.1016/s0092-8674(00)80679-0 · Cited by 275 · see citing works
Chatterjee, N., & Bohmann, D. (2012) · PLoS ONE · doi:10.1371/journal.pone.0034063 · Cited by 254 · see citing works
Oncogenic Ras Diverts a Host TNF Tumor Suppressor Activity into Tumor Promoter
Cordero, J. B., Macagno, J. P., Stefanatos, R. K. A., Strathdee, K. E., Cagan, R. L., & Vidal, M. (2010) · Developmental Cell · doi:10.1016/j.devcel.2010.05.014 · Cited by 239 · see citing works
Golembo, M., Schweitzer, R., Freeman, M., & Shilo, B. (1996) · Development · doi:10.1242/dev.122.1.223 · Cited by 230 · see citing works
Cell cycling and patterned cell proliferation in the wing primordium of Drosophila.
Milán, M., Campuzano, S., & Garcı́a-Bellido, A. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.2.640 · Cited by 228 · see citing works
Differential mitotic rates and patterns of growth in compartments in the Drosophila wing
Simpson, P., & Morata, G. (1981) · Developmental Biology · doi:10.1016/0012-1606(81)90261-x · Cited by 228 · see citing works
Malignant Drosophila Tumors Interrupt Insulin Signaling to Induce Cachexia-like Wasting
Figueroa-Clarevega, A., & Bilder, D. H. (2015) · Developmental Cell · doi:10.1016/j.devcel.2015.03.001 · Cited by 223 · see citing works
Schnepp, B., Grumbling, G. B., Donaldson, T. D., & Simcox, A. A. (1996) · Genes & Development · doi:10.1101/gad.10.18.2302 · Cited by 214 · see citing works
Ghiglione, C., Carraway, K. L., Amundadottir, L. T., Boswell, R. E., Perrimon, N., & Duffy, J. B. (1999) · Cell · doi:10.1016/s0092-8674(00)80594-2 · Cited by 206 · see citing works
In vivo analysis of Yorkie phosphorylation sites
Oh, H., & Irvine, K. D. (2009) · Oncogene · doi:10.1038/onc.2009.43 · Cited by 196 · see citing works
Competitive Interactions Between Cells: Death, Growth, and Geography
Johnston, L. A. (2009) · Science · doi:10.1126/science.1163862 · Cited by 194 · see citing works
Díaz‐Benjumea, F. J., & Hafen, E. (1994) · Development · doi:10.1242/dev.120.3.569 · Cited by 192 · see citing works
Tumor suppression by cell competition through regulation of the Hippo pathway
Chen, C.-L., Schroeder, M. C., Kango-Singh, M., Tao, C., & Halder, G. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1113882109 · Cited by 187 · see citing works
Parameters of cell competition in the compartments of the wing disc of Drosophila
Simpson, P. (1979) · Developmental Biology · doi:10.1016/0012-1606(79)90284-7 · Cited by 183 · see citing works
Vidal, M., Larson, D. E., & Cagan, R. L. (2006) · Developmental Cell · doi:10.1016/j.devcel.2005.11.007 · Cited by 173 · see citing works
The ligand Sas and its receptor PTP10D drive tumour-suppressive cell competition
Yamamoto, M., Ohsawa, S., Kunimasa, K., & Igaki, T. (2017) · Nature · doi:10.1038/nature21033 · Cited by 157 · see citing works
Boggiano, J. C., & Fehon, R. G. (2012) · Developmental Cell · doi:10.1016/j.devcel.2012.03.013 · Cited by 140 · see citing works
Modeling Human Cancers in Drosophila
Sonoshita, M., & Cagan, R. L. (2016) · Current topics in developmental biology/Current Topics in Developmental Biology · doi:10.1016/bs.ctdb.2016.07.008 · Cited by 138 · see citing works
Cellular Organization and Cytoskeletal Regulation of the Hippo Signaling Network
Sun, S., & Irvine, K. D. (2016) · Trends in Cell Biology · doi:10.1016/j.tcb.2016.05.003 · Cited by 135 · see citing works
Buff, E. M., Carmena, A., Gisselbrecht, S. S., Jiménez, F., & Michelson, A. M. (1998) · Development · doi:10.1242/dev.125.11.2075 · Cited by 131 · see citing works
The transcriptional response to tumorigenic polarity loss in Drosophila
Bunker, B. D., Nellimoottil, T. T., Boileau, R. M., Classen, A. K., & Bilder, D. (2015) · eLife · doi:10.7554/elife.03189 · Cited by 114 · see citing works
Musacchio, M., & Perrimon, N. (1996) · Developmental Biology · doi:10.1006/dbio.1996.0198 · Cited by 113 · see citing works
Analysis of twenty‐four Gal4 lines in Drosophila melanogaster
Hrdlicka, L., Gibson, M. C., Kiger, A. A., Micchelli, C. A., Schöber, M., Schöck, F., & Perrimon, N. (2002) · genesis · doi:10.1002/gene.10125 · Cited by 106 · see citing works
Subdivision of theDrosophilawing imaginal disc by EGFR-mediated signaling
Zecca, M., & Struhl, G. (2002) · Development · doi:10.1242/dev.129.6.1357 · Cited by 99 · see citing works
Pinal, N., Calleja, M., & Morata, G. (2019) · Open Biology · doi:10.1098/rsob.180256 · Cited by 99 · see citing works
In vivo genetic dissection of tumor growth and the Warburg effect
Wang, C., Purkayastha, A., Jones, K. T., Thaker, S. K., & Banerjee, U. K. (2016) · eLife · doi:10.7554/elife.18126 · Cited by 90 · see citing works
GLAD: an Online Database of G ene L ist A nnotation for D rosophila
Hu, Y., Comjean, A., Perkins, L. A., Perrimon, N., & Mohr, S. E. (2015) · Journal of Genomics · doi:10.7150/jgen.12863 · Cited by 80 · see citing works
Slit-Robo Repulsive Signaling Extrudes Tumorigenic Cells from Epithelia
Vaughen, J., & Igaki, T. (2016) · Developmental Cell · doi:10.1016/j.devcel.2016.11.015 · Cited by 79 · see citing works
Control of growth and patterning of theDrosophilawing imaginal disc by EGFR-mediated signaling
Zecca, M., & Struhl, G. (2002) · Development · doi:10.1242/dev.129.6.1369 · Cited by 75 · see citing works
Cosolo, A., Jaiswal, J., Csordás, G., Grass, I., Uhlířová, M., & Classen, A.-K. (2019) · eLife · doi:10.7554/elife.41036 · Cited by 67 · see citing works
Ghiglione, C., Amundadottir, L. T., Andrésdóttir, M. B., Bilder, D. H., Diamonti, J. A., Noselli, S., Perrimon, N., & Carraway, K. L. (2003) · Development · doi:10.1242/dev.00617 · Cited by 64 · see citing works
A Drosophila Tumor Suppressor Gene Prevents Tonic TNF Signaling through Receptor N-Glycosylation
de Vreede, G., Morrison, H. A., Houser, A. M., Boileau, R. M., Andersen, D. S., Colombani, J., & Bilder, D. H. (2018) · Developmental Cell · doi:10.1016/j.devcel.2018.05.012 · Cited by 58 · see citing works
Dissecting Social Cell Biology and Tumors Using Drosophila Genetics
Pastor-Pareja, J. C., & Xu, T. (2013) · Annual Review of Genetics · doi:10.1146/annurev-genet-110711-155414 · Cited by 57 · see citing works
Warburg Effect Metabolism Drives Neoplasia in a Drosophila Genetic Model of Epithelial Cancer
Eichenlaub, T., Villadsen, R., Freitas, F. C. D. P., Andrējeva, D., Aldana, B. I., Nguyen, T., PETERSEN, O. W., Gorodkin, J., Herranz, H., & Cohen, S. M. (2018) · Current Biology · doi:10.1016/j.cub.2018.08.035 · Cited by 42 · see citing works
Modelling Cooperative Tumorigenesis in Drosophila
Richardson, H. E., & Portela, M. (2018) · BioMed Research International · doi:10.1155/2018/4258387 · Cited by 38 · see citing works
Live Imaging of Neuroblast Lineages within Intact Larval Brains in DrosophilaPreprint
Cabernard, C., & Doe, C. Q. (2013) · Cold Spring Harbor Protocols · doi:10.1101/pdb.prot078162 · Cited by 31 · see citing works
Self-citation
Flagged first, then by citations
1 of the 67 references couldn’t be matched to a known paper.
Cited by
Sorted by citations
Two-Faced: Roles of JNK Signalling During Tumourigenesis in the Drosophila Model
La Marca, J. E., & Richardson, H. E. (2020) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2020.00042 · Cited by 139 · see citing works
Single‐cell RNA sequencing in Drosophila: Technologies and applications
Li, H. (2020) · Wiley Interdisciplinary Reviews Developmental Biology · doi:10.1002/wdev.396 · Cited by 52 · see citing works
Worley, M. I., Everetts, N. J., Yasutomi, R., Chang, R. J., Saretha, S., Yosef, N., & Hariharan, I. K. (2022) · Current Biology · doi:10.1016/j.cub.2022.06.040 · Cited by 48 · see citing works
Epithelial monitoring through ligand-receptor segregation ensures malignant cell elimination
de Vreede, G., Gerlach, S. U., & Bilder, D. H. (2022) · Science · doi:10.1126/science.abl4213 · Cited by 47 · see citing works
Deng, M., Wang, Y., Zhang, L., Yang, Y., Huang, S., Wang, J., Ge, H., Ishibashi, T., & Yan, Y. (2019) · Development · doi:10.1242/dev.179754 · Cited by 44 · see citing works
Self-citationMechanism of tumor‐suppressive cell competition in flies
Kanda, H., & Igaki, T. (2020) · Cancer Science · doi:10.1111/cas.14575 · Cited by 38 · see citing works
Isolation and RNA sequencing of single nuclei from Drosophila tissues
McLaughlin, C. N., Qi, Y., Quake, S. R., Luo, L., & Li, H. (2022) · STAR Protocols · doi:10.1016/j.xpro.2022.101417 · Cited by 36 · see citing works
Shared enhancer gene regulatory networks between wound and oncogenic programs
Floc'hlay, S., Balaji, R., Stanković, D., Christiaens, V. M., Bravo González-Blas, C., De Winter, S., Hulselmans, G. J., De Waegeneer, M., Quan, X., Koldere, D., et al. (2023) · eLife · doi:10.7554/elife.81173 · Cited by 27 · see citing works
Metabolic reprogramming in cancer: mechanistic insights from Drosophila
Wong, K. K. L., & Verheyen, E. M. (2021) · Disease Models & Mechanisms · doi:10.1242/dmm.048934 · Cited by 19 · see citing works
Afadin couples RAS GTPases to the polarity rheostat Scribble
Goudreault, M., Gagné, V., Jo, C. H., Singh, S., Killoran, R. C., Gingras, A., & Smith, M. J. (2022) · Nature Communications · doi:10.1038/s41467-022-32335-8 · Cited by 16 · see citing works
Defining bone fide effectors of RAS GTPases
Smith, M. J. (2023) · BioEssays · doi:10.1002/bies.202300088 · Cited by 12 · see citing works
Cell-cell interactions that drive tumorigenesis in Drosophila
Enomoto, M., & Igaki, T. (2022) · Fly · doi:10.1080/19336934.2022.2148828 · Cited by 9 · see citing works
Wong, K. K. L., Liao, J. Z., Shih, C. R. Y., Harden, N., & Verheyen, E. M. (2020) · Journal of Cell Science · doi:10.1242/jcs.250944 · Cited by 10 · see citing works
Critical genetic program for Drosophila imaginal disc regeneration revealed by single-cell analysisPreprint
Worley, M. I., Everetts, N. J., Yasutomi, R., Yosef, N., & Hariharan, I. K. (2021) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2021.07.08.451678 · Cited by 2 · see citing works
Mitotic polarity oscillation promotes epithelial tumor progressionPreprint
Jeyanathan, G., Cao, M., Pellikka, M., Robinson, S., Talukder, P., Ghorayeb, V., & Tepaß, U. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.02.06.636979 · Cited by 2 · see citing works
Waghmare, I., Gangwani, K., Rai, A., Singh, A., & Kango-Singh, M. (2023) · doi:10.1101/2023.10.18.561369 · Cited by 1 · see citing works
Metabolic Adaptations in Cancer and the Host Using Drosophila Models and Advanced Tools
Saez-Carrion, E., Aguilar‐Aragon, M., García-López, L., Domínguez, M., & Uribe, M. L. (2024) · Cells · doi:10.3390/cells13231977 · Cited by 1 · see citing works
Oncogenic Ras, Yki and Notch signals converge to confer clone competitiveness through Upd2
Wang, Y., Huang, R., Deng, M., He, J., Deng, M., Ishibashi, T., Yu, C., Zhai, Z., & Yan, Y. (2025) · Journal of genetics and genomics/Journal of Genetics and Genomics · doi:10.1016/j.jgg.2025.04.017 · Cited by 1 · see citing works
Self-citationWen, J., Sai, K., Masutani, S., Aoshima, Y., Yumi, K., Kyo, T., Hasegawa, J., Itoh, T., Mizuta, K., Nakamura, T., et al. (2026) · Nature Communications · doi:10.1038/s41467-026-73504-3 · Cited by 1 · see citing works
First person – Tiantian Ji and Lina Zhang
(2019) · Disease Models & Mechanisms · doi:10.1242/dmm.041798
Waghmare, I., Gangwani, K., Rai, A., Singh, A., & Kango‐Singh, M. (2024) · Cancers · doi:10.3390/cancers16091768 · Cited by 1 · see citing works
Chen, Z., Zhang, X., Deng, M., Li, C., Nguyen, T. T., Liu, M., Dou, K., Ishibashi, T., Wang, J., & Yan, Y. (2025) · Disease Models & Mechanisms · doi:10.1242/dmm.052313
Self-citationChen, Z., Zhang, X., Deng, M., Li, C., Nguyen, T. T., Liu, M., Dou, K., Ishibashi, T., Wang, J., & Yan, Y. (2025) · doi:10.14711/thesis-hdl152380
Self-citationYang, C., Yang, Y., Liu, Z. T., Bai, X., 马晓慧, Tang, J., Huang, R., Liao, Y., Liu, Y., Wen, L., et al. (2026) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2601991123
Self-citationJo, C. H., Strakhova, R., Goudreault, M., Astrain, G. B., & Smith, M. J. (2026) · Biochemical Journal · doi:10.1042/bcj20260336
- Authors
- Ji, T., Zhang, L., Deng, M., Huang, S., Wang, Y., Pham, T. T., Smith, A. A., Sridhar, V., Cabernard, C., Wang, J., & Yan, Y.
- Affiliations
- Hong Kong University of Science and Technology (HK)
- University of Washington (US)
- Corresponding author
- Yan, Yan
- Venue
- Disease Models & Mechanisms
- Publisher
- The Company of Biologists
- Published
- 2019-08-01
- Volume
- 12
- Issue
- 8
- ISSN
- 1754-8403 (ISSN-L)
- 1754-8411
- PMC
- PMC6737955
- OpenAlex
- W2966503042
- Cited by
- 25
- References
- 67
- Citations by year
- 2026: 3 · 2025: 4 · 2024: 2 · 2023: 3 · 2022: 5 · 2021: 2 · 2020: 4 · 2019: 2
- FWCI
- 1.07
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Disease Models & Mechanisms (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Rare & Special e-Zone (The Hong Kong University of Science and Technology) (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- HighWire Press Open Archive (submittedVersion)
- Funders
- Research Grants Council, University Grants Committee (GRF16103815, 16104018, 16150016, AoE/M-09/12, N_HKUST606/17, 26102719, C6002-17GF, C7065-18GF)
- Shenzhen Science and Technology Innovation Commission (JCYJ20170306161537148, JCYJ20180223181229868)
- Innovation and Technology Commission - Hong Kong (ITCPD/17-9, ITS/480/18FP)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Melanoma and MAPK Pathways
- Keywords
- Scribble, MAPK signaling, JNK signaling, ERK signaling, tumor plasticity, intratumoral heterogeneity, G2/M cell cycle arrest, tumor growth kinetics, single-cell transcriptomics
- MeSH terms
- Animals, Drosophila melanogaster, Membrane Proteins, Mutation, Neoplasms, Time Factors, MAP Kinase Signaling System, Drosophila Proteins, Cell Proliferation, Cell Cycle Checkpoints, Transcriptome
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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