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Cited by 653Cell Adhesion Molecules ResearchHER2/EGFR in Cancer ResearchCellular Mechanics and Interactions

Reciprocal interactions between β1-integrin and epidermal growth factor receptor in three-dimensional basement membrane breast cultures: A different perspective in epithelial biology

Open access
Wang, Fei, Weaver, Valerie M., Petersen, Ole W., Larabell, Carolyn A., Dedhar, Shoukat, Briand, Per, Lupu, Ruth, Bissell, Mina J.·1998·Proceedings of the National Academy of Sciences
DOI 10.1073/pnas.95.25.14821PMC PMC24533
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Abstract

Anchorage and growth factor independence are cardinal features of the transformed phenotype. Although it is logical that the two pathways must be coregulated in normal tissues to maintain homeostasis, this has not been demonstrated directly. We showed previously that down-modulation of β1-integrin signaling reverted the malignant behavior of a human breast tumor cell line (T4–2) derived from phenotypically normal cells (HMT-3522) and led to growth arrest in a three-dimensional (3D) basement membrane assay in which the cells formed tissue-like acini (14). Here, we show that there is a bidirectional cross-modulation of β1-integrin and epidermal growth factor receptor (EGFR) signaling via the mitogen-activated protein kinase (MAPK) pathway. The reciprocal modulation does not occur in monolayer (2D) cultures. Antibody-mediated inhibition of either of these receptors in the tumor cells, or inhibition of MAPK kinase, induced a concomitant down-regulation of both receptors, followed by growth-arrest and restoration of normal breast tissue morphogenesis. Cross-modulation and tissue morphogenesis were associated with attenuation of EGF-induced transient MAPK activation. To specifically test EGFR and β1-integrin interdependency, EGFR was overexpressed in nonmalignant cells, leading to disruption of morphogenesis and a compensatory up-regulation of β1-integrin expression, again only in 3D. Our results indicate that when breast cells are spatially organized as a result of contact with basement membrane, the signaling pathways become coupled and bidirectional. They further explain why breast cells fail to differentiate in monolayer cultures in which these events are mostly uncoupled. Moreover, in a subset of tumor cells in which these pathways are misregulated but functional, the cells could be “normalized” by manipulating either pathway.

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Crossref · 10.1073/pnas.95.25.14821

Cites

42 of 42 references verified0 citation errors · 0 not checkable

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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?

  • Wan et al. experiments revealed that pseudopods extending from cells could encroach into pits in culture surfaces; less rigid pseudopods could act as anchors and influence migration patterns, providing contact guidance.

    “The effect of microtopography on cell migration was further supported by Wan et al. (113), whose experiments also revealed that pseudopods extending from cells could encroach into pits in culture surfaces.The less rigid pseudopods could act as anchors for the cell and influence its migration patterns, thereby providing a contact guidance (113).”

    From Modeling physiological events in 2D vs. 3D cell culture (2017) · cites this paper as [113]

    The Abstract describes β1-integrin and EGFR signaling in three-dimensional breast-cell cultures, not migration over patterned surfaces. Searches for pseudopods, pits, microtopography, anchors, and contact guidance found no passage addressing the attributed experiments. The cited paper is by Wang et al., whereas the citing sentence names Wan et al. (LLM, conf=0.75)

    Experimental — accuracy not yet measured

  • Surface attachment efficiency was higher on rounded surfaces compared with smooth surfaces.

    “The efficiency of the surface attachment was also shown to be higher on rounded surfaces compared with smooth surfaces.”

    From Modeling physiological events in 2D vs. 3D cell culture (2017) · cites this paper as [113]

    The Materials and Methods passage describes breast-cell cultures on plastic, collagen-coated dishes, and in basement membrane, but does not compare attachment to rounded and smooth surfaces. A search for surface attachment efficiency and that shape comparison found no passage addressing the claim. Page numbers were not available in our copy. (LLM, conf=0.76)

    Experimental — accuracy not yet measured

  • Wan et al. demonstrated that cells preferred to round up on smooth-surfaced PLLA substrates and stretch on rough surfaces.

    “They demonstrated that cells preferred to round up on smooth-surfaced PLLA substrates and stretch on rough surfaces.”

    From Modeling physiological events in 2D vs. 3D cell culture (2017) · cites this paper as [113]

    The Materials and Methods section describes breast cells cultured in basement membrane, and the Abstract discusses integrin–EGFR signaling. Searches for PLLA, surface roughness, and rounded versus stretched cells found no passage addressing the claimed substrate comparison. (LLM, conf=0.75)

    Experimental — accuracy not yet measured

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Cites

Flagged first, then by citations

Research works printed but not linked: 7

  1. Petersen, O. W., Ronnov-Jessen, L., Howlett, A. R. & Bissell, M. J. (1992) Proc. Natl. Acad. Sci. USA 89, 9064-9068.
  2. Okamoto, S. & Oka, T. (1984) Proc. Natl. Acad. Sci. USA 81, 6059-6063.
  3. Fowler, K. J., Walker, F., Alexander, W., Hibbs, M. L., Nice, E. C., Bohmer, R. M., Mann, G. B., Thumwood, C., Maglitto, R. & Danks, J. A. (1995) Proc. Natl. Acad. Sci. USA 92, 1465-1469.
  4. Huang, H. S., Nagane, M., Klingbeil, C. K., Lin, H., Nishikawa, R., Ji, X. D., Huang, C. M., Gill, G. N., Wiley, H. S. & Cavenee, W. K. (1997) J. Biol. Chem. 272, 2927-2935.
  5. Damsky, C. H., Librach, C., Lim, K. H., Fitzgerald, M. L., McMaster, M. T., Janatpour, M., Zhou, Y., Logan, S. K. & Fisher, S. J. (1994) Development (Cambridge, U.K.) 120, 3657-3666.
  6. Delcommenne, M., Tan, C., Gray, V., Ruel, L., Woodgett, J. & Dedhar, S. (1998) Proc. Natl. Acad. Sci. USA 95, 11211-11216.
  7. Sivaraman, V. S., Wang, H., Nuovo, G. J. & Malbon, C. C. (1997) J. Clin. Invest. 99, 1478-1483. 14826 Cell Biology: Wang et al. Proc. Natl. Acad. Sci. USA 95 (1998)

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Authors
Wang, F., Weaver, V. M., Petersen, O. W., Larabell, C. A., Dedhar, S., Briand, P., Lupu, R., & Bissell, M. J.
Affiliations
Lawrence Berkeley National Laboratory (US)
Corresponding author
Bissell, Mina J.
ORCID
Venue
Proceedings of the National Academy of Sciences
Publisher
National Academy of Sciences
Published
1998-12-08
Volume
95
Issue
25
Pages
14821-14826
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
DOI
10.1073/pnas.95.25.14821
PMC
PMC24533
OpenAlex
W2165022280
Cited by
653
References
42
Citations by year
2026: 4 · 2025: 10 · 2024: 7 · 2023: 8 · 2022: 11 · 2021: 29 · 2020: 20 · 2019: 12 · 2018: 22 · 2017: 25 · 2016: 18 · 2015: 32 · 2014: 33 · 2013: 36 · 2012: 34
FWCI
5.63
Type
journal article
Language
en
Open access
Locations
  • Proceedings of the National Academy of Sciences (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • eScholarship (California Digital Library) (submittedVersion)
Funders
  • U.S. Department of Energy (DE-AC03-?, AC03-76SF00098, DEAC03-76SF00098, Contract DE-AC03-76SF00098)
  • Kræftens Bekæmpelse
  • Sundhed og Sygdom, Det Frie Forskningsråd
  • National Institutes of Health (DE-AC03- 76SF00098)
  • Medical Research Council
  • National Cancer Institute (CA-64786, R37CA064786, R01CA064786)
  • Biological and Environmental Research
Topics
  • Health Sciences › Medicine › Immunology and Allergy › Cell Adhesion Molecules Research
  • Health Sciences › Medicine › Oncology › HER2/EGFR in Cancer Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular Mechanics and Interactions
Keywords
beta1 integrin, epidermal growth factor receptor, MAPK signaling, basement membrane, 3D cell culture, breast tumor cells, tissue morphogenesis, anchorage-independent growth
MeSH terms
Basement Membrane, Breast, Cell Line, Epithelial Cells, Female, Humans, Protein Binding, Protein Conformation, Integrin beta1, ErbB Receptors

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