The DOI matches its Crossref record; 16 of the 16 references it cites were found in a registry or an index.
Genotype tunes pancreatic ductal adenocarcinoma tissue tension to induce matricellular fibrosis and tumor progression
Open accessAbstract
Fibrosis compromises pancreatic ductal carcinoma (PDAC) treatment and contributes to patient mortality, yet antistromal therapies are controversial. We found that human PDACs with impaired epithelial transforming growth factor-β (TGF-β) signaling have high epithelial STAT3 activity and develop stiff, matricellular-enriched fibrosis associated with high epithelial tension and shorter patient survival. In several KRAS-driven mouse models, both the loss of TGF-β signaling and elevated β1-integrin mechanosignaling engaged a positive feedback loop whereby STAT3 signaling promotes tumor progression by increasing matricellular fibrosis and tissue tension. In contrast, epithelial STAT3 ablation attenuated tumor progression by reducing the stromal stiffening and epithelial contractility induced by loss of TGF-β signaling. In PDAC patient biopsies, higher matricellular protein and activated STAT3 were associated with SMAD4 mutation and shorter survival. The findings implicate epithelial tension and matricellular fibrosis in the aggressiveness of SMAD4 mutant pancreatic tumors and highlight STAT3 and mechanics as key drivers of this phenotype.
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Cites
Role of YAP/TAZ in mechanotransduction
Dupont, S., Morsut, L., Aragona, M., Enzo, E., Giulitti, S., Cordenonsi, M., Zanconato, F., Le Digabel, J., Forcato, M., Bicciato, S., et al. (2011) · Nature · doi:10.1038/nature10137 · Cited by 5,979
Comprehensive molecular profiling of lung adenocarcinoma
The Cancer Genome Atlas Research Network (2014) · Nature · doi:10.1038/nature13385 · Cited by 5,732
Özdemir, B. C., Pentcheva-Hoang, T., Carstens, J. L., Zheng, X., Wu, C.-C., Simpson, T. R., Laklai, H., Sugimoto, H., Kahlert, C., Novitskiy, S. V., et al. (2014) · Cancer Cell · doi:10.1016/j.ccr.2014.04.005 · Cited by 2,681
Self-citationProvenzano, P. P., Cuevas, C., Chang, A. E., Goel, V. K., Von Hoff, D. D., & Hingorani, S. R. (2012) · Cancer Cell · doi:10.1016/j.ccr.2012.01.007 · Cited by 2,195
Moffitt, R. A., Marayati, R., Flate, E. L., Volmar, K. E., Loeza, S. G. H., Hoadley, K. A., Rashid, N. U., Williams, L. A., Eaton, S. C., Chung, A. H., et al. (2015) · Nature Genetics · doi:10.1038/ng.3398 · Cited by 2,194
Self-citationThe Role of Mechanical Forces in Tumor Growth and Therapy
Jain, R. K., Martin, J. D., & Stylianopoulos, T. (2014) · Annual Review of Biomedical Engineering · doi:10.1146/annurev-bioeng-071813-105259 · Cited by 1,044 · cited 2×
“Rather, the elevated tissue mechanics directly activate key pathways such as integrin-dependent signaling and YAP to promote tumor progression and aggression 10–12 .”
BackgroundAguirre, A. J., Bardeesy, N., Sinha, M., Lopez, L., Tuveson, D. A., Horner, J., Redston, M. S., & DePinho, R. A. (2003) · Genes & Development · doi:10.1101/gad.1158703 · Cited by 1,033
Chauhan, V. P., Martin, J. D., Liu, H., Lacorre, D. A., Jain, S. R., Kozin, S. V., Stylianopoulos, T., Mousa, A. S., Han, X., Adstamongkonkul, P., et al. (2013) · Nature Communications · doi:10.1038/ncomms3516 · Cited by 1,031
Hippo Pathway Activity Influences Liver Cell Fate
Yimlamai, D., Christodoulou, C., Galli, G. G., Yanger, K., Pepe-Mooney, B., Gurung, B., Shrestha, K., Cahan, P., Stanger, B. Z., & Camargo, F. D. (2014) · Cell · doi:10.1016/j.cell.2014.03.060 · Cited by 857
KRAS and YAP1 Converge to Regulate EMT and Tumor Survival
Shao, D. D., Xue, W., Krall, E. B., Bhutkar, A., Piccioni, F., Wang, X., Schinzel, A. C., Sood, S., Rosenbluh, J., Kim, J. W., et al. (2014) · Cell · doi:10.1016/j.cell.2014.06.004 · Cited by 744
Lymphatic and interstitial flow in the tumour microenvironment: linking mechanobiology with immunity
Swartz, M. A., & Lund, A. W. (2012) · Nature Reviews Cancer · doi:10.1038/nrc3186 · Cited by 544
ROCK and JAK1 Signaling Cooperate to Control Actomyosin Contractility in Tumor Cells and Stroma
Sanz-Moreno, V., Gaggioli, C., Yeo, M., Albrengues, J., Wallberg, F., Viros, A., Hooper, S., Mitter, R., Féral, C. C., Cook, M., et al. (2011) · Cancer Cell · doi:10.1016/j.ccr.2011.06.018 · Cited by 409
Alonzi, T., Maritano, D., Gorgoni, B., Rizzuto, G., Libert, C., & Poli, V. (2001) · Molecular and Cellular Biology · doi:10.1128/mcb.21.5.1621-1632.2001 · Cited by 329
Self-citationYachida, S., White, C. M., Naito, Y., Zhong, Y., Brosnan, J. A., Macgregor-Das, A. M., Morgan, R. A., Saunders, T., Laheru, D. A., Herman, J. M., et al. (2012) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-12-1215 · Cited by 280
Self-citationIjichi, H., Chytil, A., Gorska, A. E., Aakre, M. E., Bierie, B., Tada, M., Mohri, D., Miyabayashi, K., Asaoka, Y., Maeda, S., et al. (2011) · Journal of Clinical Investigation · doi:10.1172/jci42754 · Cited by 256 · cited 2×
“G-protein-coupled-receptor-mediated Janus kinase (JAK) activation stimulates activation of both signal transducer and activator of transcription-3 (STAT3) and ROCK1 and induces acto-myosin-mediated cell contractility, and STAT3 has been implicated in PDACs 41–45 .”
BackgroundInfluentialSelf-citationBarbieri, I., Pensa, S., Pannellini, T., Quaglino, E., Maritano, D., Demaria, M., Voster, A., Turkson, J., Cavallo, F., Watson, C. J., et al. (2010) · Cancer Research · doi:10.1158/0008-5472.can-09-2840 · Cited by 148
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Elyada, E., Bolisetty, M., Laise, P., Flynn, W. F., Courtois, E. T., Burkhart, R. A., Teinor, J. A., Belleau, P., Biffi, G., Lucito, M. S., et al. (2019) · Cancer Discovery · doi:10.1158/2159-8290.cd-19-0094 · Cited by 2,241
Concepts of extracellular matrix remodelling in tumour progression and metastasis
Winkler, J., Abisoye-Ogunniyan, A., Metcalf, K. J., & Werb, Z. (2020) · Nature Communications · doi:10.1038/s41467-020-18794-x · Cited by 2,296
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Hamidi, H., & Ivaska, J. (2018) · Nature Reviews Cancer · doi:10.1038/s41568-018-0038-z · Cited by 1,493
Biffi, G., Oni, T. E., Spielman, B., Hao, Y., Elyada, E., Park, Y., Preall, J., & Tuveson, D. A. (2019) · Cancer Discovery · doi:10.1158/2159-8290.cd-18-0710 · Cited by 1,360
Metadata
- Authors
- Laklai, H., Miroshnikova, Y. A., Pickup, M. W., Collisson, E. A., Kim, G. E., Barrett, A. S., Hill, R. C., Lakins, J. N., Schlaepfer, D. D., Mouw, J. K., LeBleu, V. S., Roy, N., Novitskiy, S. V., Johansen, J. S., Poli, V., Kalluri, R., Iacobuzio-Donahue, C. A., Wood, L. D., Hebrok, M., Hansen, K., Moses, H. L., & Weaver, V. M.
- Venue
- Nature Medicine
- Published
- 2016-04-18
- Volume
- 22
- Issue
- 5
- Pages
- 497-505
- ISSN
- 1078-8956 (ISSN-L)
- 1546-170X
- OpenAlex
- W2337683177
- Cited by
- 603
- References
- 16
- FWCI
- 28.12
- Type
- journal article
- Language
- en
- Open access
- green
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