Evidence map›Paper›PMID 28973887›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2017

Cross-activating c-Met/β1 integrin complex drives metastasis and invasive resistance in cancer.

Arman Jahangiri, Alan Nguyen, Ankush Chandra, Maxim K Sidorov, Garima Yagnik, Jonathan Rick, Sung Won Han, William Chen, Patrick M Flanigan, Dina Schneidman-Duhovny and 10 more

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers.

0numbers the graph read from it
0cells of the map it votes in
61citing papers in PubMed
5.5field-weighted citation impact, top 3% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

61 citing papers in PubMed, 80 citations in OpenAlex.

  1. Article
  2. Review
  3. Beyond DNA damage: 3D tumor models and the integrin mechanobiology of radioresistance.Journal of experimental & clinical cancer research : CR · 2026
    Review
  4. Met regulates endoderm migration in zebrafish.bioRxiv : the preprint server for biology · 2026
    Article
  5. Article
  6. Review
  7. Article
  8. Article
  9. Article
  10. Review
  11. Article
  12. The MET Oncogene Network of Interacting Cell Surface Proteins.International journal of molecular sciences · 2024
    Review
  13. Article
  14. Article
  15. Review
  16. Review
  17. Review
  18. Review
  19. Review
  20. Article

1 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

20 authors at 3 institutions in 2 countries.

Arman JahangiriDepartment of Neurosurgery and Brain Tumor Research Center, University of California, San Francisco, CA 94143.
Alan NguyenDepartment of Neurosurgery and Brain Tumor Research Center, University of California, San Francisco, CA 94143.
Ankush ChandraDepartment of Neurosurgery and Brain Tumor Research Center, University of California, San Francisco, CA 94143.ORCID 0000-0003-1843-3894
Maxim K SidorovDepartment of Neurosurgery and Brain Tumor Research Center, University of California, San Francisco, CA 94143.
Garima YagnikDepartment of Neurosurgery and Brain Tumor Research Center, University of California, San Francisco, CA 94143.
Jonathan RickDepartment of Neurosurgery and Brain Tumor Research Center, University of California, San Francisco, CA 94143.
Sung Won HanDepartment of Neurosurgery and Brain Tumor Research Center, University of California, San Francisco, CA 94143.
William ChenDepartment of Neurosurgery and Brain Tumor Research Center, University of California, San Francisco, CA 94143.
Patrick M FlaniganDepartment of Neurosurgery and Brain Tumor Research Center, University of California, San Francisco, CA 94143.
Dina Schneidman-DuhovnyDepartment of Bioengineering and Therapeutic Sciences, University of California, San Francisco, CA 94143.
Smita MascharakDepartment of Neurosurgery and Brain Tumor Research Center, University of California, San Francisco, CA 94143.
Michael De LayDepartment of Neurosurgery and Brain Tumor Research Center, University of California, San Francisco, CA 94143.
Brandon ImberDepartment of Neurosurgery and Brain Tumor Research Center, University of California, San Francisco, CA 94143.
Catherine C ParkDepartment of Radiation Oncology and Breast Program, University of California, San Francisco, CA 94143.
Kunio MatsumotoCancer Research Institute, Kanazawa University, 13-1 Takaramachi, Kanazawa 920-8641, Japan.
Kan LuDepartment of Neurosurgery and Brain Tumor Research Center, University of California, San Francisco, CA 94143.
Gabriele BergersDepartment of Neurosurgery and Brain Tumor Research Center, University of California, San Francisco, CA 94143.
Andrej SaliDepartment of Bioengineering and Therapeutic Sciences, University of California, San Francisco, CA 94143.
William A WeissDepartment of Neurology, University of California, San Francisco, CA 94143.
Manish K AghiDepartment of Neurosurgery and Brain Tumor Research Center, University of California, San Francisco, CA 94143; manish.aghi@ucsf.edu.ORCID 0000-0002-2949-2227
University of California, San Francisco · USKanazawa University · JPQB3 · US

Funding

Tissue CoreP50CA097257 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Susan M Chang · 2002 to 2026
$57.4M
Tumor cell and microenvironment changes causing antiangiogenic therapy resistanceR01NS079697 · NINDS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI AGHI, MANISH · 2013 to 2021
$3.2M
Characterizing and Targeting Tumoral Factors Recruiting Perivascular ProgenitorsK02NS064167 · NINDS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI AGHI, MANISH · 2009 to 2013
$916k
beta1 integrin/c-Met: a receptor complex driving invasive resistance to anti-angiogenic therapy in glioblastomaF31CA203372 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI JAHANGIRI, ARMAN · 2016 to 2017
$66k
Howard Hughes Medical InstituteNCI NIH HHS F31 CA203372NCI NIH HHS P50 CA097257NINDS NIH HHS K02 NS064167NINDS NIH HHS R01 NS079697
6 · The paper itself

Abstract

The molecular underpinnings of invasion, a hallmark of cancer, have been defined in terms of individual mediators but crucial interactions between these mediators remain undefined. In xenograft models and patient specimens, we identified a c-Met/β1 integrin complex that formed during significant invasive oncologic processes: breast cancer metastases and glioblastoma invasive resistance to antiangiogenic VEGF neutralizing antibody, bevacizumab. Inducing c-Met/β1 complex formation through an engineered inducible heterodimerization system promoted features crucial to overcoming stressors during metastases or antiangiogenic therapy: migration in the primary site, survival under hypoxia, and extravasation out of circulation. c-Met/β1 complex formation was up-regulated by hypoxia, while VEGF binding VEGFR2 sequestered c-Met and β1 integrin, preventing their binding. Complex formation promoted ligand-independent receptor activation, with integrin-linked kinase phosphorylating c-Met and crystallography revealing the c-Met/β1 complex to maintain the high-affinity β1 integrin conformation. Site-directed mutagenesis verified the necessity for c-Met/β1 binding of amino acids predicted by crystallography to mediate their extracellular interaction. Far-Western blotting and sequential immunoprecipitation revealed that c-Met displaced α5 integrin from β1 integrin, creating a complex with much greater affinity for fibronectin (FN) than α5β1. Thus, tumor cells adapt to microenvironmental stressors induced by metastases or bevacizumab by coopting receptors, which normally promote both cell migration modes: chemotaxis, movement toward concentrations of environmental chemoattractants, and haptotaxis, movement controlled by the relative strengths of peripheral adhesions. Tumor cells then redirect these receptors away from their conventional binding partners, forming a powerful structural c-Met/β1 complex whose ligand-independent cross-activation and robust affinity for FN drive invasive oncologic processes.

Indexed as

Drug Resistance, NeoplasmAngiogenesis InhibitorsAnimalsApoptosisBevacizumabBreast NeoplasmsCell AdhesionCell MovementFemaleFibronectinsGlioblastomaHumansIntegrin beta1MiceNeoplasm InvasivenessPhosphorylationAngiogenesis InhibitorsBevacizumabFibronectinsIntegrin beta1MET protein, humanProto-Oncogene Proteins c-metangiogenesisglioblastomahypoxiainvasionresistance

Identifiers

PMID28973887
PMCPMC5642678
OpenAlexW2760276067

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.