ArticleOncotarget2015
Mucin1 shifts Smad3 signaling from the tumor-suppressive pSmad3C/p21(WAF1) pathway to the oncogenic pSmad3L/c-Myc pathway by activating JNK in human hepatocellular carcinoma cells.
Article in Oncotarget, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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.
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.
Who cites it
18 citing papers in PubMed, 26 citations in OpenAlex.
- Tanshinone IIA alleviates liver fibrosis by suppressing hepatic stellate cell proliferation via ERK/cyclin D1/p-Smad3L signaling axis.Iranian journal of basic medical sciences · 2025Article
- The multifaceted role of MUC1 in tumor therapy resistance.Clinical and experimental medicine · 2023Review
- Whole-exome sequencing identifies a set of genes as markers of hepatocellular carcinoma early recurrence.Hepatology international · 2023Article
- Review
- Alpha-Fetoprotein Binding Mucin and Scavenger Receptors: An Available Bio-Target for Treating Cancer.Frontiers in oncology · 2021Review
- Knockdown of SMAD3 inhibits the growth and enhances the radiosensitivity of lung adenocarcinoma via p21International journal of biological sciences · 2020Article
- Genetic interactions between the DBL-1/BMP-like pathway andMolecular biology of the cell · 2019Article
- Review
- Cathepsin L-mediated resistance of paclitaxel and cisplatin is mediated by distinct regulatory mechanisms.Journal of experimental & clinical cancer research : CR · 2019Article
- Mucins: the Old, the New and the Promising Factors in Hepatobiliary Carcinogenesis.International journal of molecular sciences · 2019Review
- Profilin-1 deficiency leads to SMAD3 upregulation and impaired 3D outgrowth of breast cancer cells.British journal of cancer · 2018Article
- Hepatocyte Growth Factor Regulates the miR-206-HDAC4 Cascade to Control Neurogenic Muscle Atrophy following Surgical Denervation in Mice.Molecular therapy. Nucleic acids · 2018Article
- Article
- Targeting MUC1 and JNK by RNA interference and inhibitor inhibit the development of hepatocellular carcinoma.Cancer science · 2017Article
- Role of C-Jun N-terminal Kinase in Hepatocellular Carcinoma Development.Targeted oncology · 2016Review
- Functional Consequences of Differential O-glycosylation of MUC1, MUC4, and MUC16 (Downstream Effects on Signaling).Biomolecules · 2016Review
- Article
- Cytotoxicity of various types of gold-mesoporous silica nanoparticles in human breast cancer cells.International journal of nanomedicine · 2015Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mucin1 (MUC1) is a transmembrane glycoprotein that acts as an oncogene in human hepatic tumorigenesis. Hepatocellular carcinoma (HCC) cells often gain advantage by reducing the tumor-suppressive activity of transforming growth factor beta (TGF-β) together with stimulation of its oncogenic activity as in MUC1 expressing HCC cells; however, molecular mechanisms remain largely unknown. Type I TGF-β receptor (TβRI) and c-Jun NH2-terminal kinase (JNK) differentially phosphorylate Smad3 mediator to create 2 phosphorylated forms: COOH-terminally phosphorylated Smad3 (pSmad3C) and linker-phosphorylated Smad3 (pSmad3L). Here, we report that MUC1 overexpression in HCC cell lines suppresses TβRI-mediated pSmad3C signaling which involves growth inhibition by up-regulating p21(WAF1). Instead, MUC1 directly activates JNK to stimulate oncogenic pSmad3L signaling, which fosters cell proliferation by up-regulating c-Myc. Conversely, MUC1 gene silencing in MUC1 expressing HCC cells results in preserved tumor-suppressive function via pSmad3C, while eliminating pSmad3L-mediated oncogenic activity both in vitro and in vivo. In addition, high correlation between MUC1 and pSmad3L/c-Myc but not pSmad3C/p21(WAF1) expression was observed in HCC tissues from patients. Collectively, these results indicate that MUC1 shifts Smad3 signaling from a tumor-suppressive pSmad3C/p21(WAF1) to an oncogenic pSmad3L/c-Myc pathway by directly activating JNK in HCC cells, suggesting that MUC1 is an important target for HCC therapy.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.