Evidence map›Paper›PMID 39578442›Full record

ArticleCell death & disease2024

Complex IIa formation and ABC transporters determine sensitivity of OSCC to Smac mimetics.

Yuhan Wang, Zijian Liu, Qian Si, Wanqiu Lu, Yuxian Song, Wanyong Jin, Xihu Yang, Zihui Li, Xinyang Hu, Liang Ding and 8 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell death & disease, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
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

3 citing papers in PubMed.

  1. Review
  2. Review
  3. Article
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

18 authors.

Yuhan WangCentral Laboratory of Stomatology, Nanjing Stomatological Hospital, Affiliated Hospital of Medical School, Research Institute of Stomatology, Nanjing University, Nanjing, China.ORCID 0009-0001-7859-8394
Zijian LiuCentral Laboratory of Stomatology, Nanjing Stomatological Hospital, Affiliated Hospital of Medical School, Research Institute of Stomatology, Nanjing University, Nanjing, China.
Qian SiCentral Laboratory of Stomatology, Nanjing Stomatological Hospital, Affiliated Hospital of Medical School, Research Institute of Stomatology, Nanjing University, Nanjing, China.
Wanqiu LuSchool of Biopharmacy, China Pharmaceutical University, Nanjing, Jiangsu, China.
Yuxian SongCentral Laboratory of Stomatology, Nanjing Stomatological Hospital, Affiliated Hospital of Medical School, Research Institute of Stomatology, Nanjing University, Nanjing, China.
Wanyong JinCentral Laboratory of Stomatology, Nanjing Stomatological Hospital, Affiliated Hospital of Medical School, Research Institute of Stomatology, Nanjing University, Nanjing, China.
Xihu YangDepartment of Oral and Maxillofacial Surgery, Affiliated Hospital of Jiangsu University, Zhenjiang, China.
Zihui LiCentral Laboratory of Stomatology, Nanjing Stomatological Hospital, Affiliated Hospital of Medical School, Research Institute of Stomatology, Nanjing University, Nanjing, China.
Xinyang HuCentral Laboratory of Stomatology, Nanjing Stomatological Hospital, Affiliated Hospital of Medical School, Research Institute of Stomatology, Nanjing University, Nanjing, China.
Liang DingCentral Laboratory of Stomatology, Nanjing Stomatological Hospital, Affiliated Hospital of Medical School, Research Institute of Stomatology, Nanjing University, Nanjing, China.
Yue JingCentral Laboratory of Stomatology, Nanjing Stomatological Hospital, Affiliated Hospital of Medical School, Research Institute of Stomatology, Nanjing University, Nanjing, China.
Pei WengCentral Laboratory of Stomatology, Nanjing Stomatological Hospital, Affiliated Hospital of Medical School, Research Institute of Stomatology, Nanjing University, Nanjing, China.
Qiuya YuCentral Laboratory of Stomatology, Nanjing Stomatological Hospital, Affiliated Hospital of Medical School, Research Institute of Stomatology, Nanjing University, Nanjing, China.
Lorraine A O'ReillyThe Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, 3052, Australia.ORCID 0000-0001-7134-6496
John SilkeThe Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, 3052, Australia.ORCID 0000-0002-7611-5774
Xiaoxin ZhangCentral Laboratory of Stomatology, Nanjing Stomatological Hospital, Affiliated Hospital of Medical School, Research Institute of Stomatology, Nanjing University, Nanjing, China. 693216371@qq.com.ORCID 0009-0007-1743-0989
Qingang HuDepartment of Oral and Maxillofacial Surgery, Nanjing Stomatological Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China. qghu@nju.edu.cn.
Yanhong NiCentral Laboratory of Stomatology, Nanjing Stomatological Hospital, Affiliated Hospital of Medical School, Research Institute of Stomatology, Nanjing University, Nanjing, China. Yanhong.Ni@nju.edu.cn.ORCID 0000-0002-3890-3884

Funding

National Natural Science Foundation of China (National Science Foundation of China) 82173159, 82002865National Natural Science Foundation of China (National Science Foundation of China) 82173380
6 · The paper itself

Abstract

Small molecule inhibitors of apoptosis proteins (IAPs) antagonists, known as Smac mimetics (SMs), activate non-canonical NF-κB and sensitize cancer cells to TNF-induced cell death. SMs are currently in phase III clinical trials for head and neck squamous cell carcinoma (HNSCC) after promising phase II trials. To explore the utility of SMs in oral squamous cell carcinoma (OSCC), we tested nine human OSCC cell lines and correlated SM sensitivity with both IAP mutation and expression levels. cIAP1 protein expression was shown to be higher in OSCC and a predictor of poor prognosis. However, our in vitro and in vivo testing demonstrated differential sensitivity to SMs, which did not correlate with cIAP1 and cIAP2 expression in these OSCC cell lines. Exogenous TNF failed to effectively increase the sensitivity of SM-resistant OSCC cells to SM-induced cell death. SM resistance was associated with a deficiency in Complex IIa formation, but activation of non-canonical NF-κB was not a determinant of SM efficacy. Finally, metabolic analysis revealed that the ABC transporter pathway was activated in SM-resistant OSSC cells, and SMs combined with ABC transporter inhibitors improved cell death sensitivity to overcome SM resistance. These studies highlight the therapeutic potential of SMs in OSCC and support patient stratification to improve efficacy with the addition of adjuvant therapy.

Indexed as

Mouth NeoplasmsAnimalsApoptosisApoptosis Regulatory ProteinsATP-Binding Cassette TransportersCarcinoma, Squamous CellCell Line, TumorDrug Resistance, NeoplasmHumansInhibitor of Apoptosis ProteinsMiceMice, NudeMitochondrial ProteinsNF-kappa BSquamous Cell Carcinoma of Head and NeckXenograft Model Antitumor AssaysApoptosis Regulatory ProteinsATP-Binding Cassette TransportersDIABLO protein, humanInhibitor of Apoptosis ProteinsMitochondrial ProteinsNF-kappa B

Identifiers

PMID39578442
PMCPMC11584628

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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.