Evidence map›Paper›PMID 42174609›Full record

ArticleJournal of translational medicine2026

Targeted suppression of SPP1 inhibits tumor invasion and metastasis in NRF2 hyperactivated cisplatin resistant HNSCC.

Mutsuki Kawabe, Sujuan Yang, Lorena I Gomez-Bolanos, Shiro Takamatsu, Sylvia Flores, Patricia D Castro, Tsung-You Tsai, Arisa Nishikawa Kaga, Kento Okamoto, Mitchell J Frederick and 4 more

Abstract read
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In one paragraph

Article in Journal of translational medicine, 2026. 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

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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.

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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

14 authors.

Mutsuki Kawabe *Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX, 77030-4009, USA.
Sujuan YangDepartment of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Lorena I Gomez-BolanosDepartment of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Shiro TakamatsuDepartment of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Sylvia FloresDepartment of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX, 77030-4009, USA.
Patricia D CastroDepartment of Otolaryngology-Head and Neck Surgery, Baylor College of Medicine, Houston, TX, USA.
Tsung-You TsaiDepartment of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX, 77030-4009, USA.
Arisa Nishikawa KagaDepartment of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX, 77030-4009, USA.
Kento OkamotoDepartment of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX, 77030-4009, USA.
Mitchell J FrederickDepartment of Otolaryngology-Head and Neck Surgery, Baylor College of Medicine, Houston, TX, USA.
Vlad C SandulacheDepartment of Otolaryngology-Head and Neck Surgery, Baylor College of Medicine, Houston, TX, USA.
Humam KadaraDepartment of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Jeffrey N Myers *Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX, 77030-4009, USA. jmyers@mdanderson.org.
Abdullah A Osman *Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX, 77030-4009, USA. aaosman@mdanderson.org.

Funding

Tumor Model and Biospecimen Repository CoreU54CA274321 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI Jeffrey Nicholas Myers, VLAD C SANDULACHE · 2022 to 2026
$7.7M
NCI NIH HHS U54 CA274321NCI NIH HHS U54CA274321
6 · The paper itself

Abstract

backgroundCisplatin remains the standard systemic therapy for the definitive treatment of head and neck squamous cell carcinoma (HNSCC), however, resistance to cisplatin continues to be a major barrier to effective treatment, particularly in tumors with NRF2 hyperactivation. Recent studies identify secreted phosphoprotein 1 (SPP1/osteopontin) as a key NRF2 target frequently overexpressed in cancers, where it drives aggressive tumor behavior, metastasis, chemoresistance, and, in some cases, immune suppression. Our recent data highlight SPP1 as one of the top 10 NRF2-upregulated genes in cisplatin-resistant HNSCC. However, its specific role in therapy resistance and metastasis in HNSCC remains unclear. Here, we investigate whether targeting SPP1 can suppress tumor aggressiveness and improve cisplatin response in HNSCC.

methodsUsing established human HNSCC cell lines and mouse models, we utilized conventional western blotting, cell invasion, functional proteomics and high resolution spatial transcriptomics to examine the role of SPP1 in driving tumor progression and metastasis in therapy-resistant HNSCC.

resultsTargeted suppression of SPP1 improved cisplatin sensitivity, inhibited tumor invasion and metastasis both in vitro and in vivo and reduced expression of several metastatic signaling proteins in NRF2-hyperactivated HNSCC. Proteomic analysis revealed that silencing SPP1 led to dysregulation of critical oncogenic and metastatic signaling pathways, including MAPK, AKT/mTOR, FAK, and PAK1. Spatial transcriptomic analysis uncovered a potential mechanistic interaction between SPP1, integrins and CD44 receptors in both primary and metastatic HNSCC. Spatial annotation and enrichment analyses using HALLMARK revealed gene set signatures of interferon and EMT present in cell clusters with SPP1 expression in both the primary tumor and lung metastases. Finally, increased expression of SPP1 was found to be poor prognostic factor and significantly correlated with NFE2L2/KEAP1 mutational status and higher tumor grade in HNSCC patients.

conclusionsTargeting dysregulated SPP1 improved cisplatin sensitivity and suppressed tumor invasion and metastasis in NRF2-hyperactivated HNSCC, underscoring the therapeutic potential of SPP1 inhibitors to improve patient outcomes.

Indexed as

CisplatinDrug Resistance, NeoplasmHead and Neck NeoplasmsNF-E2-Related Factor 2OsteopontinSquamous Cell Carcinoma of Head and NeckAnimalsCell Line, TumorGene Expression Regulation, NeoplasticHumansKelch-Like ECH-Associated Protein 1MiceMice, NudeNeoplasm InvasivenessNeoplasm MetastasisSignal TransductionCisplatinKelch-Like ECH-Associated Protein 1NFE2L2 protein, humanNF-E2-Related Factor 2OsteopontinSPP1 protein, humanCD44CDDPCisplatinHead and neck cancerIntegrinsKEAP1NRF2OsteopontinSPP1

Identifiers

PMID42174609
PMCPMC13383472

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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.