CoChat
Sign Up
Cited by 41Maternal and fetal healthcarePregnancy and preeclampsia studiesReproductive System and Pregnancy

Up-regulated cytotrophoblast DOCK4 contributes to over-invasion in placenta accreta spectrum

Open access
McNally, Leah, Zhou, Yan, Robinson, Joshua F., Zhao, Guangfeng, Chen, Lee-may, Chen, Hao, Kim, M. Yvonne, Kapidzic, Mirhan +3 more·2020·Proceedings of the National Academy of Sciences
DOI 10.1073/pnas.1920776117PMC PMC7355036
Open this paper in CoChat — free account

Abstract

Significance: The syndrome of cytotrophoblast invasion beyond the normal boundary (in the superficial myometrium) is collectively termed placenta accreta spectrum. The incidence of this condition is rising. However, little is known about the underlying molecular changes. Global transcriptomic profiling of cytotrophoblasts isolated from these cases, as compared to gestational age-matched controls, revealed numerous changes in gene expression involving diverse pathways, including cell signaling, migration, and immune functions. DOCK4 was the most highly up-regulated mRNA in the cases. Mutations in this gene are mechanistically linked to cancer progression. Overexpression of DOCK4 in primary cytotrophoblasts increased their invasiveness. This study provides molecular insights into the pathways driving placenta accreta spectrum and suggests numerous future directions.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1073/pnas.1920776117

Cites

1 of 1 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Research works printed but not linked: 52

  1. [1]N. M. Hunkapiller, S. J. Fisher, Chapter 12. Placental remodeling of the uterine vasculature. Methods Enzymol. 445, 281– 302 (2008). 19022064 PMC2857511
  2. [2]M. C. Lacroix., Stimulation of human trophoblast invasion by placental growth hormone. Endocrinology 146, 2434– 2444 (2005). 15718272
  3. [3]K. Red-Horse., EPHB4 regulates chemokine-evoked trophoblast responses: A mechanism for incorporating the human placenta into the maternal circulation. Development 132, 4097– 4106 (2005). 16107476
  4. [4]R. Pijnenborg, L. Vercruysse, M. Hanssens, The uterine spiral arteries in human pregnancy: Facts and controversies. Placenta 27, 939– 958 (2006). 16490251
  5. [5]C. Ferretti, L. Bruni, V. Dangles-Marie, A. P. Pecking, D. Bellet, Molecular circuits shared by placental and cancer cells, and their implications in the proliferative, invasive and migratory capacities of trophoblasts. Hum. Reprod. Update 13, 121– 141 (2007). 17068222
  6. [6]B. Novakovic, R. Saffery, Placental pseudo-malignancy from a DNA methylation perspective: Unanswered questions and future directions. Front. Genet. 4, 285 (2013). 24368911 PMC3857887
  7. [7]E. Maltepe, A. I. Bakardjiev, S. J. Fisher, The placenta: Transcriptional, epigenetic, and physiological integration during development. J. Clin. Invest. 120, 1016– 1025 (2010). 20364099 PMC2846055
  8. [8]M. J. Hendrix, E. A. Seftor, A. R. Hess, R. E. Seftor, Vasculogenic mimicry and tumour-cell plasticity: Lessons from melanoma. Nat. Rev. Cancer 3, 411– 421 (2003). 12778131
  9. [9]E. Wagenblast., A model of breast cancer heterogeneity reveals vascular mimicry as a driver of metastasis. Nature 520, 358– 362 (2015). 25855289 PMC4634366
  10. [10]W. A. Goh, I. Zalud, Placenta accreta: Diagnosis, management and the molecular biology of the morbidly adherent placenta. J. Matern. Fetal Neonatal Med. 29, 1795– 1800 (2016). 26135782 PMC5424888
  11. [11]E. Jauniaux, S. Collins, G. J. Burton, Placenta accreta spectrum: Pathophysiology and evidence-based anatomy for prenatal ultrasound imaging. Am. J. Obstet. Gynecol. 218, 75– 87 (2018). 28599899
  12. [12]Anonymous, Obstetric care consensus No. 7: Placenta accreta spectrum. Obstet. Gynecol. 132, e259– e275 (2018). 30461695
  13. [13]H. C. Bartels., Association of implementing a multidisciplinary team approach in the management of morbidly adherent placenta with maternal morbidity and mortality. Obstet. Gynecol. 132, 1167– 1176 (2018). 30234729
  14. [14]A. G. Eller., Maternal morbidity in cases of placenta accreta managed by a multidisciplinary care team compared with standard obstetric care. Obstet. Gynecol. 117, 331– 337 (2011). 21309195
  15. [15]A. A. Shamshirsaz., Outcomes of planned compared with urgent deliveries using a multidisciplinary team approach for morbidly adherent placenta. Obstet. Gynecol. 131, 234– 241 (2018). 29324609
  16. [16]S. Lurie, M. Glezerman, The history of cesarean technique. Am. J. Obstet. Gynecol. 189, 1803– 1806 (2003). 14710118
  17. [17]T. Eshkoli, A. Y. Weintraub, R. Sergienko, E. Sheiner, Placenta accreta: Risk factors, perinatal outcomes, and consequences for subsequent births. Am. J. Obstet. Gynecol. 208, 219.e1- 219.e7 (2013). 23313722
  18. [18]G. Zeevi., The risk of placenta accreta following primary cesarean delivery. Arch. Gynecol. Obstet. 297, 1151– 1156 (2018). 29404741
  19. [19]V. Yajnik., DOCK4, a GTPase activator, is disrupted during tumorigenesis. Cell 112, 673– 684 (2003). 12628187
  20. [20]G. Gadea, A. Blangy, Dock-family exchange factors in cell migration and disease. Eur. J. Cell Biol. 93, 466– 477 (2014). 25022758
  21. [21]Y. Zhou., Comparative analysis of maternal-fetal interface in preeclampsia and preterm labor. Cell Tissue Res. 329, 559– 569 (2007). 17549520
  22. [22]T. J. Chen., CDK-associated Cullin 1 promotes cell proliferation with activation of ERK1/2 in human lung cancer A549 cells. Biochem. Biophys. Res. Commun. 437, 108– 113 (2013). 23806693
  23. [23]S. Kuchay., PTEN counteracts FBXL2 to promote IP3R3- and Ca2+-mediated apoptosis limiting tumour growth. Nature 546, 554– 558 (2017). 28614300 PMC5627969
  24. [24]L. Zhang., Microenvironment-induced PTEN loss by exosomal microRNA primes brain metastasis outgrowth. Nature 527, 100– 104 (2015). 26479035 PMC4819404
  25. [25]J. Haybaeck., A lymphotoxin-driven pathway to hepatocellular carcinoma. Cancer Cell 16, 295– 308 (2009). 19800575 PMC4422166
  26. [26]F. Liu., Long noncoding RNA FTX inhibits hepatocellular carcinoma proliferation and metastasis by binding MCM2 and miR-374a. Oncogene 35, 5422– 5434 (2016). 27065331
  27. [27]L. Yuan., A novel correlation between ATP5A1 gene expression and progression of human clear cell renal cell carcinoma identified by co-expression analysis. Oncol. Rep. 39, 525– 536 (2018). 29207195 PMC5783621
  28. [28]E. K. Greuber, P. Smith-Pearson, J. Wang, A. M. Pendergast, Role of ABL family kinases in cancer: From leukaemia to solid tumours. Nat. Rev. Cancer 13, 559– 571 (2013). 23842646 PMC3935732
  29. [29]F. O. Kok, I. T. Shepherd, H. I. Sirotkin, Churchill and Sip1a repress fibroblast growth factor signaling during zebrafish somitogenesis. Dev. Dyn. 239, 548– 558 (2010). 20034103 PMC2962425
  30. [30]L. A. Bach, IGFBP-6 five years on; not so “forgotten”? Growth Horm. IGF Res. 15, 185– 192 (2005). 15914054
  31. [31]J. W. Purcell., LRRC15 is a novel mesenchymal protein and stromal target for antibody-drug conjugates. Cancer Res. 78, 4059– 4072 (2018). 29764866
  32. [32]A. Kanai., Identification of DOCK4 and its splicing variant as PIP3 binding proteins. IUBMB Life 60, 467– 472 (2008). 18459162
  33. [33]J. A. Westbrook., Identification and validation of DOCK4 as a potential biomarker for risk of bone metastasis development in patients with early breast cancer. J. Pathol. 247, 381– 391 (2019). 30426503 PMC6618075
  34. [34]J. R. Yu., TGF-β/Smad signaling through DOCK4 facilitates lung adenocarcinoma metastasis. Genes Dev. 29, 250– 261 (2015). 25644601 PMC4318142
  35. [35]S. Abraham., A Rac/Cdc42 exchange factor complex promotes formation of lateral filopodia and blood vessel lumen morphogenesis. Nat. Commun. 6, 7286 (2015). 26129894 PMC4507007
  36. [36]W. D. Mahauad-Fernandez, K. A. DeMali, A. K. Olivier, C. M. Okeoma, Bone marrow stromal antigen 2 expressed in cancer cells promotes mammary tumor growth and metastasis. Breast Cancer Res. 16, 493 (2014). 25499888 PMC4308845
  37. [37]W. Liu, Y. Cao, Y. Guan, C. Zheng, BST2 promotes cell proliferation, migration and induces NF-κB activation in gastric cancer. Biotechnol. Lett. 40, 1015– 1027 (2018). 29774441
  38. [38]L. W. Qiu., Abnormal expression of angiopoietin-2 associated with invasion, metastasis and prognosis of lung cancer [in Chinese]. Zhonghua Yi Xue Za Zhi 98, 1261– 1266 (2018). 29747316
  39. [39]T. Kawashima., Oligodendrocytes up-regulate the invasive activity of glioblastoma cells via the angiopoietin-2 signaling pathway. Anticancer Res. 39, 577– 584 (2019). 30711932
  40. [40]A. Sureshbabu., IGFBP5 induces cell adhesion, increases cell survival and inhibits cell migration in MCF-7 human breast cancer cells. J. Cell Sci. 125, 1693– 1705 (2012). 22328518
  41. [41]K. J. Wright., An ARL3-UNC119-RP2 GTPase cycle targets myristoylated NPHP3 to the primary cilium. Genes Dev. 25, 2347– 2360 (2011). 22085962 PMC3222901
  42. [42]K. Hua, R. J. Ferland, Primary cilia proteins: Ciliary and extraciliary sites and functions. Cell. Mol. Life Sci. 75, 1521– 1540 (2018). 29305615 PMC5899021
  43. [43]C. M. Szalinski, A. Labilloy, J. R. Bruns, O. A. Weisz, VAMP7 modulates ciliary biogenesis in kidney cells. PLoS One 9, e86425 (2014). 24466086 PMC3899255
  44. [44]D. J. Sharp, J. L. Ross, Microtubule-severing enzymes at the cutting edge. J. Cell Sci. 125, 2561– 2569 (2012). 22595526 PMC3403230
  45. [45]I. Sánchez, B. D. Dynlacht, Cilium assembly and disassembly. Nat. Cell Biol. 18, 711– 717 (2016). 27350441 PMC5079433
  46. [47]G. Pagani., Diagnostic accuracy of ultrasound in detecting the severity of abnormally invasive placentation: A systematic review and meta-analysis. Acta Obstet. Gynecol. Scand. 97, 25– 37 (2018). 28963728
  47. [48]M. A. Herron, M. Katz, R. K. Creasy, Evaluation of a preterm birth prevention program: Preliminary report. Obstet. Gynecol. 59, 452– 456 (1982). 7078897
  48. [49]Y. Zhou., Reversal of gene dysregulation in cultured cytotrophoblasts reveals possible causes of preeclampsia. J. Clin. Invest. 123, 2862– 2872 (2013). 23934129 PMC3999620
  49. [51]W. Huang, B. T. Sherman, R. A. Lempicki, Bioinformatics enrichment tools: Paths toward the comprehensive functional analysis of large gene lists. Nucleic Acids Res. 37, 1– 13 (2009). 19033363 PMC2615629
  50. [52]Y. Zhou., Vascular endothelial growth factor ligands and receptors that regulate human cytotrophoblast survival are dysregulated in severe preeclampsia and hemolysis, elevated liver enzymes, and low platelets syndrome. Am. J. Pathol. 160, 1405– 1423 (2002). 11943725 PMC3277330
  51. [53]O. Genbacev., Integrin α4-positive human trophoblast progenitors: Functional characterization and transcriptional regulation. Hum. Reprod. 31, 1300– 1314 (2016). 27083540 PMC4871193
  52. [54]T. Garrido-Gomez., Severe pre-eclampsia is associated with alterations in cytotrophoblasts of the smooth chorion. Development 144, 767– 777 (2017). 28232601 PMC5374356

Cited by

Sorted by citations

Authors
McNally, L., Zhou, Y., Robinson, J. F., Zhao, G., Chen, L.-M., Chen, H., Kim, M. Y., Kapidzic, M., Gormley, M., Hannibal, R., & Fisher, S. J.
Affiliations
  • University of California, San Francisco (US)
  • Stanford Medicine (US)
Corresponding author
Fisher, Susan J.
ORCID
Venue
Proceedings of the National Academy of Sciences
Publisher
National Academy of Sciences
Published
2020-06-23
Volume
117
Issue
27
Pages
15852-15861
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
DOI
10.1073/pnas.1920776117
PMC
PMC7355036
OpenAlex
W3037504912
Cited by
41
References
1
Citations by year
2026: 2 · 2025: 6 · 2024: 15 · 2023: 5 · 2022: 2 · 2021: 10 · 2020: 1
FWCI
4.32
Type
journal article
Language
en
Open access
Licence
Locations
  • Proceedings of the National Academy of Sciences (publishedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • eScholarship (California Digital Library) (submittedVersion)
  • eScholarship (California Digital Library) (submittedVersion, cc-by-nc-nd)
Funders
NIH (HD076253)
Topics
  • Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Maternal and fetal healthcare
  • Health Sciences › Medicine › Obstetrics and Gynecology › Pregnancy and preeclampsia studies
  • Life Sciences › Immunology and Microbiology › Immunology › Reproductive System and Pregnancy
Keywords
placenta accreta spectrum, DOCK4, cytotrophoblast, trophoblast invasion, myometrium, gene expression profiling, placental pathology, trophoblast migration, immune function, signal transduction
MeSH terms
Female, Gene Expression Regulation, Humans, Myometrium, Placenta, Placenta Accreta, Pre-Eclampsia, Pregnancy, Trophoblasts, Uterus, Up-Regulation, GTPase-Activating Proteins, 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 ›

Are you an author, or do you see a problem with this page? Request a review