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@ARTICLE{Zhu:293309,
author = {Y. Zhu and S. N. Kim and Z.-R. Chen and R. Will$^*$ and
R.-D. Zhong and P. Dammann and U. Sure},
title = {{PDCD}10 {I}s a {K}ey {P}layer in {TMZ}-{R}esistance and
{T}umor {C}ell {R}egrowth: {I}nsights into {I}ts
{U}nderlying {M}echanism in {G}lioblastoma {C}ells.},
journal = {Cells},
volume = {13},
number = {17},
issn = {2073-4409},
address = {Basel},
publisher = {MDPI},
reportid = {DKFZ-2024-01867},
pages = {1442},
year = {2024},
abstract = {Overcoming temozolomide (TMZ)-resistance is a major
challenge in glioblastoma therapy. Therefore, identifying
the key molecular player in chemo-resistance becomes urgent.
We previously reported the downregulation of PDCD10 in
primary glioblastoma patients and its tumor suppressor-like
function in glioblastoma cells. Here, we demonstrate that
the loss of PDCD10 causes a significant TMZ-resistance
during treatment and promotes a rapid regrowth of tumor
cells after treatment. PDCD10 knockdown upregulated MGMT, a
key enzyme mediating chemo-resistance in glioblastoma,
accompanied by increased expression of DNA mismatch repair
genes, and enabled tumor cells to evade TMZ-induced
cell-cycle arrest. These findings were confirmed in
independent models of PDCD10 overexpressing cells.
Furthermore, PDCD10 downregulation led to the
dedifferentiation of glioblastoma cells, as evidenced by
increased clonogenic growth, the upregulation of
glioblastoma stem cell (GSC) markers, and enhanced
neurosphere formation capacity. GSCs derived from PDCD10
knockdown cells displayed stronger TMZ-resistance and
regrowth potency, compared to their parental counterparts,
indicating that PDCD10-induced stemness may independently
contribute to tumor malignancy. These data provide evidence
for a dual role of PDCD10 in tumor suppression by
controlling both chemo-resistance and dedifferentiation, and
highlight PDCD10 as a potential prognostic marker and target
for combination therapy with TMZ in glioblastoma.},
keywords = {Humans / Glioblastoma: pathology / Glioblastoma: genetics /
Glioblastoma: metabolism / Glioblastoma: drug therapy /
Temozolomide: pharmacology / Drug Resistance, Neoplasm:
genetics / Drug Resistance, Neoplasm: drug effects / Cell
Line, Tumor / Apoptosis Regulatory Proteins: metabolism /
Apoptosis Regulatory Proteins: genetics / Gene Expression
Regulation, Neoplastic: drug effects / Neoplastic Stem
Cells: metabolism / Neoplastic Stem Cells: pathology /
Neoplastic Stem Cells: drug effects / Brain Neoplasms:
pathology / Brain Neoplasms: genetics / Brain Neoplasms:
metabolism / Brain Neoplasms: drug therapy / Membrane
Proteins: metabolism / Membrane Proteins: genetics /
Proto-Oncogene Proteins: metabolism / Proto-Oncogene
Proteins: genetics / Cell Proliferation: drug effects / DNA
Modification Methylases: metabolism / DNA Modification
Methylases: genetics / Tumor Suppressor Proteins: metabolism
/ Tumor Suppressor Proteins: genetics / DNA Repair Enzymes:
metabolism / DNA Repair Enzymes: genetics / MGMT and MMR
genes (Other) / acquired TMZ-resistance (Other) /
glioblastoma (GBM) (Other) / programmed cell death 10
(PDCD10) (Other) / stemness (Other) / Temozolomide (NLM
Chemicals) / Apoptosis Regulatory Proteins (NLM Chemicals) /
PDCD10 protein, human (NLM Chemicals) / Membrane Proteins
(NLM Chemicals) / Proto-Oncogene Proteins (NLM Chemicals) /
DNA Modification Methylases (NLM Chemicals) / MGMT protein,
human (NLM Chemicals) / Tumor Suppressor Proteins (NLM
Chemicals) / DNA Repair Enzymes (NLM Chemicals)},
cin = {W111},
ddc = {570},
cid = {I:(DE-He78)W111-20160331},
pnm = {312 - Funktionelle und strukturelle Genomforschung
(POF4-312)},
pid = {G:(DE-HGF)POF4-312},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:39273014},
pmc = {pmc:PMC11394141},
doi = {10.3390/cells13171442},
url = {https://inrepo02.dkfz.de/record/293309},
}