ArticleMolecular biology of the cell2012
Attenuation of TGF-β signaling suppresses premature senescence in a p21-dependent manner and promotes oncogenic Ras-mediated metastatic transformation in human mammary epithelial cells.
Article in Molecular biology of the cell, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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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.
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Who cites it
25 citing papers in PubMed, 45 citations in OpenAlex.
- Dual signaling pathways of TGF-β superfamily cytokines in hepatocytes: balancing liver homeostasis and disease progression.Frontiers in pharmacology · 2025Review
- PSmad3+/Olig2- expression defines a subpopulation ofFrontiers in neuroscience · 2023Article
- The functional multipotency of transforming growth factor β signaling at the intersection of senescence and cancer.Cellular and molecular life sciences : CMLS · 2022Review
- Senescence-Associated miRNAs and Their Role in Pancreatic Cancer.Pathology oncology research : POR · 2022Review
- Review
- FGF-2 induces a failure of cell cycle progression in cells harboring amplified K-Ras, revealing new insights into oncogene-induced senescence.Molecular omics · 2021Article
- Autocrine TGF-β in Cancer: Review of the Literature and Caveats in Experimental Analysis.International journal of molecular sciences · 2021Review
- Ras Signaling in Breast Cancer.Advances in experimental medicine and biology · 2021Article
- A prospect of cell immortalization combined with matrix microenvironmental optimization strategy for tissue engineering and regeneration.Cell & bioscience · 2019Review
- Long-Term In Vitro Expansion of Epithelial Stem Cells Enabled by Pharmacological Inhibition of PAK1-ROCK-Myosin II and TGF-β Signaling.Cell reports · 2018Article
- Epithelial cell senescence: an adaptive response to pre-carcinogenic stresses?Cellular and molecular life sciences : CMLS · 2017Review
- TGF-β-Dependent Growth Arrest and Cell Migration in Benign and Malignant Breast Epithelial Cells Are Antagonistically Controlled by Rac1 and Rac1b.International journal of molecular sciences · 2017Article
- TGF-β Family Signaling in the Control of Cell Proliferation and Survival.Cold Spring Harbor perspectives in biology · 2017Review
- Conserved genes and pathways in primary human fibroblast strains undergoing replicative and radiation induced senescence.Biological research · 2016Article
- Estrogen receptor alpha inhibits senescence-like phenotype and facilitates transformation induced by oncogenic ras in human mammary epithelial cells.Oncotarget · 2016Article
- Serum from Varicose Patients Induces Senescence-Related Dysfunction of Vascular Endothelium Generating Local and Systemic Proinflammatory Conditions.Oxidative medicine and cellular longevity · 2016Article
- The potential for chemical mixtures from the environment to enable the cancer hallmark of sustained proliferative signalling.Carcinogenesis · 2015Review
- Cellular senescence checkpoint function determines differential Notch1-dependent oncogenic and tumor-suppressor activities.Oncogene · 2015Article
- Sp1 regulates Raf/MEK/ERK-induced p21(CIP1) transcription in TP53-mutated cancer cells.Cellular signalling · 2015Article
- The role of cytokines in breast cancer development and progression.Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research · 2015Review
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
The molecular mechanisms that drive triple-negative, basal-like breast cancer progression are elusive. Few molecular targets have been identified for the prevention or treatment of this disease. Here we developed a series of isogenic basal-like human mammary epithelial cells (HMECs) with altered transforming growth factor-β (TGF-β) sensitivity and different malignancy, resembling a full spectrum of basal-like breast carcinogenesis, and determined the molecular mechanisms that contribute to oncogene-induced transformation of basal-like HMECs when TGF-β signaling is attenuated. We found that expression of a dominant-negative type II receptor (DNRII) of TGF-β abrogated autocrine TGF-β signaling in telomerase-immortalized HMECs and suppressed H-Ras-V12-induced senescence-like growth arrest (SLGA). Furthermore, coexpression of DNRII and H-Ras-V12 rendered HMECs highly tumorigenic and metastatic in vivo in comparison with H-Ras-V12-transformed HMECs that spontaneously escaped H-Ras-V12-induced SLGA. Microarray analysis revealed that p21 was the major player mediating Ras-induced SLGA, and attenuated or loss of p21 expression contributed to the escape from SLGA when autocrine TGF-β signaling was blocked in HMECs. Furthermore, knockdown of p21 also suppressed H-Ras-V12-induced SLGA. Our results identify that autocrine TGF-β signaling is an integral part of the cellular anti-transformation network by suppressing the expression of a host of genes, including p21-regulated genes, that mediate oncogene-induced transformation in basal-like breast cancer.
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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.