Cited by 315Cancer-related Molecular PathwaysChronic Myeloid Leukemia TreatmentsAngiogenesis and VEGF in Cancer

A Kinase-Independent Function of CDK6 Links the Cell Cycle to Tumor Angiogenesis

Open access
Kollmann, Karoline, Heller, Gerwin, Schneckenleithner, Christine, Warsch, Wolfgang, Scheicher, Ruth, Ott, Rene G., Schäfer, Markus, Fajmann, Sabine +16 more·2013·Cancer Cell

Abstract

In contrast to its close homolog CDK4, the cell cycle kinase CDK6 is expressed at high levels in lymphoid malignancies. In a model for p185BCR-ABL+ B-acute lymphoid leukemia, we show that CDK6 is part of a transcription complex that induces the expression of the tumor suppressor p16INK4a and the pro-angiogenic factor VEGF-A. This function is independent of CDK6's kinase activity. High CDK6 expression thus suppresses proliferation by upregulating p16INK4a, providing an internal safeguard. However, in the absence of p16INK4a, CDK6 can exert its full tumor-promoting function by enhancing proliferation and stimulating angiogenesis. The finding that CDK6 connects cell-cycle progression to angiogenesis confirms CDK6's central role in hematopoietic malignancies and could underlie the selection pressure to upregulate CDK6 and silence p16INK4a.

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 · 10.1016/j.ccr.2013.07.012

Cites

78 of 78 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

1 retracted

Flagged first, then by citations

3 of the 81 references couldn’t be matched to a known paper.

Cited by

Sorted by citations

Authors
Kollmann, K., Heller, G., Schneckenleithner, C., Warsch, W., Scheicher, R., Ott, R. G., Schäfer, M., Fajmann, S., Schlederer, M., Schiefer, A.-I., Reichart, U., Mayerhofer, M., Hoeller, C., Zöchbauer-Müller, S., Kerjaschki, D., Bock, C., Kenner, L., Hoefler, G., Freissmuth, M., Green, A. R., Moriggl, R., Busslinger, M., Malumbres, M., & Sexl, V.
Affiliations
  • University of Veterinary Medicine Vienna (AT)
  • Comprehensive Cancer Center Vienna (AT)
  • Research Institute of Molecular Pathology (AT)
  • Medical University of Vienna (AT)
  • Austrian Academy of Sciences (AT)
  • Ludwig Boltzmann Institute for Cancer Research (AT)
  • Wellcome/MRC Cambridge Stem Cell Institute (GB)
  • Spanish National Cancer Research Centre (ES)
Corresponding author
Sexl, Veronika
Venue
Cancer Cell
Publisher
Elsevier BV
Published
2013-08
Volume
24
Issue
2
Pages
167-181
ISSN
1535-6108 (ISSN-L)
OpenAlex
W2152600133
Cited by
313
References
81
Citations by year
2026: 16 · 2025: 22 · 2024: 27 · 2023: 23 · 2022: 35 · 2021: 33 · 2020: 42 · 2019: 25 · 2018: 20 · 2017: 20 · 2016: 17 · 2015: 19 · 2014: 10 · 2013: 4
FWCI
8.93
Type
journal article
Language
en
Update notices
erratum (2016-08-08)
Open access
Locations
  • Cancer Cell (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Funders
  • Wellcome Trust (079249, 100140)
  • Medizinische Universität Wien
Topics
  • Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
  • Health Sciences › Medicine › Hematology › Chronic Myeloid Leukemia Treatments
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Angiogenesis and VEGF in Cancer
Keywords
CDK6, CDK4, p16INK4a, VEGF-A, tumor angiogenesis, B-cell acute lymphoblastic leukemia, BCR-ABL, transcriptional regulation, cell cycle, kinase-independent function, lymphoid malignancies, cell proliferation, hematologic malignancies
MeSH terms
Animals, Cell Cycle, Humans, Mice, Inbred C57BL, Mice, Nude, Mice, Transgenic, Neoplasms, Neovascularization, Pathologic, Leukemia, B-Cell, Lymphoma, B-Cell, Cyclin-Dependent Kinase 6, Mice

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