Cited by 135Telomeres, Telomerase, and SenescenceMelanoma and MAPK PathwaysCancer-related Molecular Pathways

Microphthalmia-Associated Transcription Factor Controls the DNA Damage Response and a Lineage-Specific Senescence Program in Melanomas

Open access
Giuliano, Sandy, Cheli, Yann, Ohanna, Mickaël, Bonet, Caroline, Beuret, Laurent, Bille, Karine, Loubat, Agnès, Hofman, Véronique +5 more·2010·Cancer Research

Published version of a preprint

Abstract

Apoptosis and senescence are cellular failsafe programs that counteract excessive mitogenic signaling observed in cancer cells. Melanoma is known for its notorious resistance to apoptotic processes; therefore, senescence, which remains poorly understood in melanomas, can be viewed as a therapeutic alternative. Microphthalmia-associated transcription factor (MITF), in which its M transcript is specifically expressed in melanocyte cells, plays a critical role in melanoma proliferation, and its specific inhibition is associated with G(0)-G(1) growth arrest. Interestingly, decreased MITF expression has been described in senescent melanocytes, and we have observed an inhibition of MITF expression in melanoma cells exposed to chemotherapeutic drugs that induce their senescence. All these observations thereby question the role of MITF in controlling senescence in melanoma cells. Here, we report that long-term depletion of MITF in melanoma cells triggers a senescence program characterized by typical morphologic and biochemical changes associated with a sustained growth arrest. Further, we show that MITF-silenced cells engage a DNA damage response (DDR) signaling pathway, leading to p53 upregulation, which is critically required for senescence entry. This study uncovers the existence of a lineage-restricted DDR/p53 signaling pathway that is inhibited by MITF to prevent senescence and favor melanoma cell proliferation.

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 · 10.1158/0008-5472.can-09-2913

Cites

50 of 50 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?

  • MITF controls UVB-induced expression of pigmentation genes and DNA repair and proliferation genes in melanoma cells.

    “MITF controls UVB-induced expression of pigmentation genes32 and DNA repair and proliferation genes in melanoma cells51,52.”

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

1 of the 51 references couldn’t be matched to a known paper.

Research works printed but not linked: 2

  1. Cheli Y, Ohanna M, Ballotti R, Bertolotto C. 15-year quest in search for MITF target genes. Pigment Cell Melanoma Res 2010;23:27-40.
  2. Essner R, Kuo CT, Wang H, et al. Prognostic implications of p53 overexpression in cutaneous melanoma from sun-exposed and nonexposed sites. Cancer 1998;82:309-16.

Cited by

Sorted by citations

Authors
Giuliano, S., Cheli, Y., Ohanna, M., Bonet, C., Beuret, L., Bille, K., Loubat, A., Hofman, V., Hofman, P., Ponzio, G., Bahadoran, P., Ballotti, R., & Bertolotto, C.
Affiliations
  • Inserm (FR)
  • Authors' Affiliations: 1Institut National de la Sante et de la Recherche Medicale U895, Team 1, Biology and pathology of melanocytes: from cutaneous pigmentation to melanoma; 2University of Nice Sophia-Antipolis, UFR médecine; 3CHU NICE, Department of Dermatology; 4Institut National de la Sante et de la Recherche Medicale U634; 5ERI21/EA 4319 and Human Biobank, Nice, France
Corresponding author
Bertolotto, Corine
Venue
Cancer Research
Published
2010-04-28
Volume
70
Issue
9
Pages
3813-3822
ISSN
  • 0008-5472 (ISSN-L)
  • 1538-7445
OpenAlex
W2052677817
Cited by
135
References
51
Citations by year
2026: 3 · 2025: 3 · 2024: 5 · 2023: 3 · 2022: 7 · 2021: 15 · 2020: 7 · 2019: 11 · 2018: 8 · 2017: 13 · 2016: 10 · 2015: 15 · 2014: 7 · 2013: 9 · 2012: 6
FWCI
5.85
Type
journal article
Language
en
Open access
Locations
  • Cancer Research (publishedVersion)
  • PubMed (publishedVersion)
  • HAL (submittedVersion)
Topics
  • Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Melanoma and MAPK Pathways
  • Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
Keywords
MITF, melanoma, cellular senescence, DNA damage response, p53, transcription factors, growth arrest, apoptosis resistance, melanocyte lineage, cell proliferation
MeSH terms
Animals, DNA Damage, Humans, Melanoma, Melanoma, Experimental, Mitosis, Signal Transduction, Tumor Suppressor Protein p53, Cellular Senescence, Cell Lineage, Cell Line, Tumor, Mice, Microphthalmia-Associated Transcription Factor

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