Evidence map›Paper›PMID 41617691›Full record

ArticleNature communications2026

Cancer cachexia in STK11/LKB1-mutated non-small cell lung cancer is dependent on tumor-secreted GDF15.

Jinhai Yu, Tong Guo, Arun Gupta, Ernesto M Llano, Thomas Salisbury, Naureen Wajahat, Dianne Zhao, Sean Slater, Qing Deng, Esra A Akbay and 10 more

Abstract read
In one paragraph

Article in Nature communications, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing 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

4 citing papers in PubMed.

  1. The causes of cachexia: key signals and the brain.Nature reviews. Endocrinology · 2026
    Review
  2. Review
  3. Review
  4. Review
4 · The record

Corrections and comments

  • Update of
    2024
5 · Who and what money

Authors and funding

20 authors.

Jinhai Yu *Center for Human Nutrition, University of Texas Southwestern Medical Center, Dallas, TX, USA.ORCID 0000-0002-2992-6785
Tong Guo *Center for Human Nutrition, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Arun GuptaCenter for Human Nutrition, University of Texas Southwestern Medical Center, Dallas, TX, USA.ORCID 0000-0002-7881-9935
Ernesto M LlanoCenter for Human Nutrition, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Thomas SalisburyHamon Center for Therapeutic Oncology Research, University of Texas Southwestern Medical Center, Dallas, TX, USA.ORCID 0009-0003-5050-7221
Naureen WajahatCenter for Human Nutrition, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Dianne ZhaoCenter for Human Nutrition, University of Texas Southwestern Medical Center, Dallas, TX, USA.ORCID 0009-0000-9148-6103
Sean SlaterCenter for Human Nutrition, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Qing DengDepartment of Pathology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Esra A AkbayDepartment of Pathology, University of Texas Southwestern Medical Center, Dallas, TX, USA.ORCID 0000-0002-4149-2529
Beverly A RothermelDepartment of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, USA.ORCID 0000-0001-9037-6703
John M SheltonDepartment of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, USA.ORCID 0000-0002-2949-1638
Bret M EversDepartment of Pathology, University of Texas Southwestern Medical Center, Dallas, TX, USA.ORCID 0000-0001-5686-0315
Zhidan WuInternal Medicine Research Unit, Pfizer Inc., Cambridge, MA, USA.
Iphigenia TzameliInternal Medicine Research Unit, Pfizer Inc., Cambridge, MA, USA.
Evanthia PashosInternal Medicine Research Unit, Pfizer Inc., Cambridge, MA, USA.
James KimDepartment of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, USA.
John D MinnaHarold C. Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX, USA.ORCID 0000-0002-7776-0767
Puneeth IyengarDepartment of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, TX, USA. iyengarp@mskcc.org.ORCID 0000-0003-3740-7915
Rodney E InfanteCenter for Human Nutrition, University of Texas Southwestern Medical Center, Dallas, TX, USA. rodney.infante@utsouthwestern.edu.ORCID 0000-0003-2605-822X

Funding

X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI SELWYN M VICKERS · 1985 to 2026
$347.4M
UNIVERSITY OF TEXAS--SPORE IN LUNG CANCERP50CA070907 · NCI · UT SOUTHWESTERN MEDICAL CENTER · PI HEYMACH, JOHN V. · 1996 to 2024
$57.4M
UT Southwestern Medical Center Simmons Comprehensive Cancer CenterP30CA142543 · NCI · UT SOUTHWESTERN MEDICAL CENTER · PI Kathryn Ann O'Donnell · 2010 to 2026
$53.7M
UT Southwestern NORCP30DK127984 · NIDDK · UT SOUTHWESTERN MEDICAL CENTER · PI Jeffrey M Zigman · 2022 to 2026
$7.4M
UT GASTROENTEROLOGY/HEPATOLOGY RESEARCH TRAINING PROGRAMT32DK007745 · NIDDK · UT SOUTHWESTERN MEDICAL CENTER · PI Rodney E Infante · 1997 to 2026
$6.8M
Identifying the Cellular and Molecular Targets of JAK/STAT-Driven Adipose Wasting to Reverse Cancer CachexiaR01CA266900 · NCI · UT SOUTHWESTERN MEDICAL CENTER · PI INFANTE, RODNEY E, IYENGAR, PUNEETH · 2022 to 2025
$3.0M
LIFR-alpha/JAK/STAT3-dependent Adipose Inflammation Contributes to Obesity-Associated NAFLD - ResubmissiR01DK128166 · NIDDK · UT SOUTHWESTERN MEDICAL CENTER · PI Rodney E Infante, Puneeth Iyengar · 2022 to 2026
$2.6M
Regulation of GLI1, a synthetic lethal target of SMARCA4-deficiency, in lung adenocarcinomaR01CA258684 · NCI · UT SOUTHWESTERN MEDICAL CENTER · PI KIM, JAMES · 2021 to 2025
$1.9M
American Cancer Society (American Cancer Society, Inc.) 133889-RSG-19-195-01-TBEBurroughs Wellcome Fund (BWF) 1019692Cancer Prevention and Research Institute of Texas (Cancer Prevention Research Institute of Texas) RP210041Cancer Prevention and Research Institute of Texas (Cancer Prevention Research Institute of Texas) RP230140NCI NIH HHS P30 CA008748NCI NIH HHS R01 CA258684NCI NIH HHS R01 CA266900NIDDK NIH HHS P30 DK127984NIDDK NIH HHS R01 DK128166NIDDK NIH HHS T32 DK007745U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) 1R01CA258684U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) 1R01CA266900U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) P30CA142543U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) P50CA070907U.S. Department of Health & Human Services | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (National Institute of Diabetes & Digestive & Kidney Diseases) 1P30DK127984U.S. Department of Health & Human Services | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (National Institute of Diabetes & Digestive & Kidney Diseases) 1R01DK128166U.S. Department of Health & Human Services | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (National Institute of Diabetes & Digestive & Kidney Diseases) T32DK007745
6 · The paper itself

Abstract

Cachexia is a wasting syndrome involving adipose, muscle, and body weight loss in cancer patients. Tumor loss-of-function mutations in STK11/LKB1, a regulator of AMP-activated protein kinase, induce cancer cachexia (CC) in preclinical models and are linked to weight loss in non-small cell lung cancer (NSCLC) patients. This study examines the role of the integrated stress response (ISR) cytokine growth differentiation factor 15 (GDF15) in regulating cachexia using patient-derived and engineered STK11/LKB1-mutant NSCLC lines. Tumor cell-derived serum GDF15 levels are elevated in mice bearing these tumors. Treatment with a GDF15-neutralizing antibody or silencing GDF15 from tumor cells prevents adipose/muscle loss, strength decline, and weight reduction, identifying tumors cells as the GDF15 source. Restoring wild-type STK11/LKB1 in NSCLC lines with endogenous STK11/LKB1 loss reverses the ISR and reduces GDF15 expression rescuing the cachexia phenotype. Collectively, these findings implicate tumor-derived GDF15 as a key mediator and therapeutic target in STK11/LKB1-mutant NSCLC-associated cachexia.

Indexed as

CachexiaCarcinoma, Non-Small-Cell LungGrowth Differentiation Factor 15Lung NeoplasmsProtein Serine-Threonine KinasesAMP-Activated Protein Kinase KinasesAnimalsCell Line, TumorFemaleHumansMaleMiceMutationAMP-Activated Protein Kinase KinasesGDF15 protein, humanGrowth Differentiation Factor 15Protein Serine-Threonine KinasesSTK11 protein, human

Identifiers

PMID41617691
PMCPMC12960653

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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.