Evidence map›Paper›PMID 39191757›Full record

ArticleBone research2024

The HOXC10/NOD1/ERK axis drives osteolytic bone metastasis of pan-KRAS-mutant lung cancer.

Kun Li, Bo Yang, Yingying Du, Yi Ding, Shihui Shen, Zhengwang Sun, Yun Liu, Yuhan Wang, Siyuan Cao, Wenjie Ren and 7 more

Abstract read
In one paragraph

Article in Bone research, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing 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

9 citing papers in PubMed.

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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

17 authors.

Kun Li *Department of Musculoskeletal Oncology, Fudan University Shanghai Cancer Center, Shanghai, 200032, China.ORCID http://orcid.org/0000-0002-5863-9865
Bo Yang *School of Life Sciences, East China Normal University, Shanghai, 200241, China.
Yingying Du *School of Life Sciences, East China Normal University, Shanghai, 200241, China.
Yi DingSchool of Life Sciences, East China Normal University, Shanghai, 200241, China.
Shihui ShenSchool of Life Sciences, East China Normal University, Shanghai, 200241, China.
Zhengwang SunDepartment of Musculoskeletal Oncology, Fudan University Shanghai Cancer Center, Shanghai, 200032, China.
Yun LiuSchool of Life Sciences, East China Normal University, Shanghai, 200241, China.
Yuhan WangSchool of Life Sciences, East China Normal University, Shanghai, 200241, China.
Siyuan CaoSchool of Life Sciences, East China Normal University, Shanghai, 200241, China.
Wenjie RenSchool of Life Sciences, East China Normal University, Shanghai, 200241, China.
Xiangyu WangSchool of Life Sciences, East China Normal University, Shanghai, 200241, China.
Mengjuan LiSchool of Life Sciences, East China Normal University, Shanghai, 200241, China.
Yunpeng ZhangSchool of Life Sciences, East China Normal University, Shanghai, 200241, China.
Juan WuDepartment of Pharmacy The General Hospital of Western Theater Command, Chengdu, 610083, China.
Wei ZhengOrthopaedic Department of Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, 200233, China. wei_zheng6868@163.com.
Wangjun YanDepartment of Musculoskeletal Oncology, Fudan University Shanghai Cancer Center, Shanghai, 200032, China. wangjun_yan1234@163.com.
Lei LiChongqing Key Laboratory of Precision Optics, Chongqing Institute of East China Normal University, Chongqing, 401120, China. lli@bio.ecnu.edu.cn.

Funding

National Natural Science Foundation of China (National Science Foundation of China) 81672883National Natural Science Foundation of China (National Science Foundation of China) 82022051National Natural Science Foundation of China (National Science Foundation of China) 82303396
6 · The paper itself

Abstract

While KRAS mutation is the leading cause of low survival rates in lung cancer bone metastasis patients, effective treatments are still lacking. Here, we identified homeobox C10 (HOXC10) as a lynchpin in pan-KRAS-mutant lung cancer bone metastasis. Through RNA-seq approach and patient tissue studies, we demonstrated that HOXC10 expression was dramatically increased. Genetic depletion of HOXC10 preferentially impeded cell proliferation and migration in vitro. The bioluminescence imaging and micro-CT results demonstrated that inhibition of HOXC10 significantly reduced bone metastasis of KRAS-mutant lung cancer in vivo. Mechanistically, the transcription factor HOXC10 activated NOD1/ERK signaling pathway to reprogram epithelial-mesenchymal transition (EMT) and bone microenvironment by activating the NOD1 promoter. Strikingly, inhibition of HOXC10 in combination with STAT3 inhibitor was effective against KRAS-mutant lung cancer bone metastasis by triggering ferroptosis. Taken together, these findings reveal that HOXC10 effectively alleviates pan-KRAS-mutant lung cancer with bone metastasis in the NOD1/ERK axis-dependent manner, and support further development of an effective combinatorial strategy for this kind of disease.

Indexed as

Bone NeoplasmsHomeodomain ProteinsLung NeoplasmsMutationProto-Oncogene Proteins p21(ras)AnimalsCell Line, TumorEpithelial-Mesenchymal TransitionFemaleHumansMAP Kinase Signaling SystemMiceNod1 Signaling Adaptor ProteinOsteolysisHomeodomain ProteinsHOXC10 protein, humanKRAS protein, humanNOD1 protein, humanNod1 Signaling Adaptor ProteinProto-Oncogene Proteins p21(ras)

Identifiers

PMID39191757
PMCPMC11349752

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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.