Evidence map›Paper›PMID 38849015›Full record

ArticleCancer letters2024

BIGH3 mediates apoptosis and gap junction failure in osteocytes during renal cell carcinoma bone metastasis progression.

Tianhong Pan, Fengshuo Liu, Xiaoxin Hao, Shubo Wang, Murtaza Wasi, Jian H Song, Valerae O Lewis, Patrick P Lin, Bryan Moon, Justin E Bird and 9 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cancer letters, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing 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

5 citing papers in PubMed.

  1. Article
  2. Article
  3. Review
  4. Review
  5. Review
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

19 authors.

Tianhong PanDepartments of Orthopedic Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Fengshuo LiuDepartments of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, USA.
Xiaoxin HaoDepartments of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, USA.
Shubo WangDepartment of Mechanical Engineering, University of Delaware, Newark, DE, USA.
Murtaza WasiDepartment of Mechanical Engineering, University of Delaware, Newark, DE, USA.
Jian H SongDepartments of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Valerae O LewisDepartments of Orthopedic Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Patrick P LinDepartments of Orthopedic Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Bryan MoonDepartments of Orthopedic Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Justin E BirdDepartments of Orthopedic Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Theocharis PanaretakisDepartments of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Sue-Hwa LinDepartments of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; Departments of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Danielle WuDepartment of Diagnostic and Biomedical Sciences, The University of Texas Health Science Center at Houston, School of Dentistry, Houston, TX, USA; Departments of Bioengineering, Rice University, Houston, TX, USA.
Mary C Farach-CarsonDepartment of Diagnostic and Biomedical Sciences, The University of Texas Health Science Center at Houston, School of Dentistry, Houston, TX, USA; Departments of BioSciences, Rice University, Houston, TX, USA; Departments of Bioengineering, Rice University, Houston, TX, USA.
Liyun WangDepartment of Mechanical Engineering, University of Delaware, Newark, DE, USA.
Ningyan ZhangThe Brown Foundation Institute of Molecular Medicine, McGovern Medical School, The University of Texas Health Science Center at Houston, USA.
Zhiqiang AnThe Brown Foundation Institute of Molecular Medicine, McGovern Medical School, The University of Texas Health Science Center at Houston, USA.
Xiang H-F ZhangDepartments of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, USA; Departments of Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, TX, USA; Departments of Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX, USA; Departments of McNair Medical Institute, Baylor College of Medicine, Houston, TX, USA.
Robert L SatcherDepartments of Orthopedic Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. Electronic address: rlsatcher@mdanderson.org.

Funding

Tumor Evolution and Metastasis ProgramP30CA016672 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI DIANE BODURKA · 1985 to 2026
$290.8M
NCI NIH HHS P30 CA016672
6 · The paper itself

Abstract

Renal cell carcinoma (RCC) bone metastatis progression is driven by crosstalk between tumor cells and the bone microenvironment, which includes osteoblasts, osteoclasts, and osteocytes. RCC bone metastases (RCCBM) are predominantly osteolytic and resistant to antiresorptive therapy. The molecular mechanisms underlying pathologic osteolysis and disruption of bone homeostasis remain incompletely understood. We previously reported that BIGH3/TGFBI (transforming growth factor-beta-induced protein ig-h3, shortened to BIGH3 henceforth) secreted by colonizing RCC cells drives osteolysis by inhibiting osteoblast differentiation, impairing healing of osteolytic lesions, which is reversible with osteoanabolic agents. Here, we report that BIGH3 induces osteocyte apoptosis in both human RCCBM tissue specimens and in a preclinical mouse model. We also demonstrate that BIGH3 reduces Cx43 expression, blocking gap junction (GJ) function and osteocyte network communication. BIGH3-mediated GJ inhibition is blocked by the lysosomal inhibitor hydroxychloroquine (HCQ), but not osteoanabolic agents. Our results broaden the understanding of pathologic osteolysis in RCCBM and indicate that targeting the BIGH3 mechanism could be a combinational strategy for the treatment of RCCBM-induced bone disease that overcomes the limited efficacy of antiresorptives that target osteoclasts.

Indexed as

ApoptosisBone NeoplasmsCarcinoma, Renal CellExtracellular Matrix ProteinsGap JunctionsKidney NeoplasmsOsteocytesAnimalsbetaIG-H3 ProteinCell Line, TumorConnexin 43Disease ProgressionFemaleHumansMiceOsteolysisbetaIG-H3 ProteinConnexin 43Extracellular Matrix ProteinsGJA1 protein, humanTransforming Growth Factor betaApoptosisBIGH3/TGFBIBone metastasisOsteocyteRenal cell carcinoma

Identifiers

PMID38849015
PMCPMC11964150

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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.