Increased expression of Id1 and Id3 promotes tumorigenicity by enhancing angiogenesis and suppressing apoptosis in small cell lung cancer

Constant deregulation of Id1 and Id3 has been implicated in a wide range of carcinomas. However, underlying molecular evidence for the joint role of Id1 and Id3 in the tumorigenicity of small cell lung cancer (SCLC) is sparse. Investigating the biological significance of elevated expression in SCLC cells, we found that Id1 and Id3 co-suppression resulted in significant reduction of proliferation rate, invasiveness and anchorage-independent growth. Suppressing both Id1 and Id3 expression also greatly reduced the average size of tumors produced by transfectant cells when inoculated subcutaneously into nude mice. Further investigation revealed that suppressed expression of Id1 and Id3 was accompanied by decreased angiogenesis and increased apoptosis. Therefore, the SCLC tumorigenicity suppression effect of double knockdown of Id1 and Id3 may be regulated through pathways of apoptosis and angiogenesis.

• Publication year

  2014

• Venue

  Genes & cancer

• Publication date

  2014-05-01

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.18632/GENESANDCANCER.20PMID 25061504PMCID 4104762
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Id1 and Id3 co-expression correlates with clinical outcome in stage III-N2 non-small cell lung cancer patients treated with definitive chemoradiotherapy

  2013cited by this paper
• ID3 contributes to cerebrospinal fluid seeding and poor prognosis in medulloblastoma

  2013cited by this paper
• Id-1 is a key transcriptional regulator of glioblastoma aggressiveness and a novel therapeutic target.

  2013cited by this paper
• The hallmarks of cancer

  2012cited by this paper
• ID1 inhibits USF2 and blocks TGF-β-induced apoptosis in mesangial cells.

  2011cited by this paper
• Constitutive overexpression of Id‐1 in mammary glands of transgenic mice results in precocious and increased formation of terminal end buds, enhanced alveologenesis, delayed involution

  2011cited by this paper
• Targeting Id1 and Id3 by a specific peptide aptamer induces E-box promoter activity, cell cycle arrest, and apoptosis in breast cancer cells

  2010cited by this paper
• Inhibition of tumourigenicity of small cell lung cancer cells by suppressing Id3 expression.

  2010influential reference
• Role of inhibitor of DNA binding-1 protein is related to angiogenesis in the tumor advancement of uterine endometrial cancers.

  2010cited by this paper
• Id1/Id3 knockdown inhibits metastatic potential of pancreatic cancer.

  2010cited by this paper
• Overexpression of inhibitor of DNA-binding (ID)-1 protein related to angiogenesis in tumor advancement of ovarian cancers

  2009cited by this paper
• Triple negative breast carcinoma is a prognostic factor in Taiwanese women

  2009cited by this paper
• Increased Expression of Id Family Proteins in Small Cell Lung Cancer and its Prognostic Significance

  2008influential reference
• Proteomic approaches for serum biomarker discovery in cancer.

  2007cited by this paper
• A Randomized, Phase II Trial of Two Dose Levels of Temsirolimus (CCI-779) in Patients with Extensive-Stage Small-Cell Lung Cancer Who Have Responding or Stable Disease after Induction Chemotherapy: A Trial of the Eastern Cooperative Oncology Group (E1500)

  2007cited by this paper
• Phase III double-blind, placebo-controlled study of thalidomide in extensive-disease small-cell lung cancer after response to chemotherapy: an intergroup study FNCLCC cleo04 IFCT 00-01.

  2007cited by this paper
• Increased Id-1 expression is significantly associated with poor survival of patients with prostate cancer.

  2007cited by this paper
• ID1‐, ID2‐, and ID3‐regulated gene expression in E2A positive or negative prostate cancer cells

  2007cited by this paper
• Combination of p53 Cancer Vaccine with Chemotherapy in Patients with Extensive Stage Small Cell Lung Cancer

  2006cited by this paper
• Regulation of Angiogenesis by Id-1 through Hypoxia-Inducible Factor-1α–Mediated Vascular Endothelial Growth Factor Up-regulation in Hepatocellular Carcinoma

  2006cited by this paper
• Overexpression of Id-1 in prostate cancer cells promotes angiogenesis through the activation of vascular endothelial growth factor (VEGF).

  2005cited by this paper
• Id family of helix-loop-helix proteins in cancer

  2005cited by this paper
• Targeting Id1 and Id3 inhibits peritoneal metastasis of gastric cancer

  2005cited by this paper
• Id family of helix-loop-helix proteins in cancer

  2005cited by this paper
• Tumor Angiogenesis in Mice and Men

  2004cited by this paper
• Crucial Role of Inhibitor of DNA Binding/Differentiation in the Vascular Endothelial Growth Factor-Induced Activation and Angiogenic Processes of Human Endothelial Cells1

  2004cited by this paper
• Id family of transcription factors and vascular lesion formation.

  2004cited by this paper
• Id2 Drives Differentiation and Suppresses Tumor Formation in the Intestinal Epithelium

  2004cited by this paper
• Id-1 and Id-2 Proteins as Molecular Markers for Human Prostate Cancer Progression

  2004cited by this paper
• Overexpression of Id‐1 is associated with poor clinical outcome in node negative breast cancer

  2003cited by this paper
• Id proteins in cell growth and tumorigenesis.

  2003cited by this paper
• Level of Id-1 protein expression correlates with poor differentiation, enhanced malignant potential, and more aggressive clinical behavior of epithelial ovarian tumors.

  2003cited by this paper
• Effect of angiogenesis inhibition by Id loss and the contribution of bone-marrow-derived endothelial cells in spontaneous murine tumors.

  2003cited by this paper
• The Id proteins and angiogenesis

  2001cited by this paper
• Impaired recruitment of bone-marrow–derived endothelial and hematopoietic precursor cells blocks tumor angiogenesis and growth

  2001cited by this paper
• Id3 inhibits B lymphocyte progenitor growth and survival in response to TGF-β

  2001cited by this paper
• Id-1, ITF-2, and Id-2 Comprise a Network of Helix-Loop-Helix Proteins That Regulate Mammary Epithelial Cell Proliferation, Differentiation, and Apoptosis*

  2001cited by this paper
• Molecular markers of metastasis in breast cancer: current understanding and prospects for novel diagnosis and prevention

  2001cited by this paper
• Microquantity differential display: a strategy for a systematic analysis of differential gene expression with a small quantity of starting RNA.

  2000cited by this paper
• Id2 is a retinoblastoma protein target and mediates signalling by Myc oncoproteins

  2000cited by this paper
• Class A helix-loop-helix proteins are positive regulators of several cyclin-dependent kinase inhibitors' promoter activity and negatively affect cell growth.

  2000cited by this paper
• Lactation defect in mice lacking the helix–loop–helix inhibitor Id2

  2000cited by this paper
• ID helix-loop-helix proteins in cell growth, differentiation and tumorigenesis.

  2000cited by this paper
• Cancer statistics, 2000

  2000cited by this paper
• Id proteins are dynamically expressed in normal epidermis and dysregulated in squamous cell carcinoma.

  2000cited by this paper
• Vascular endothelial cell growth factor-induced tissue factor expression in endothelial cells is mediated by EGR-1.

  1999cited by this paper
• Massive Apoptosis of Thymocytes in T-Cell-Deficient Id1 Transgenic Mice

  1999cited by this paper
• Id1 and Id3 are required for neurogenesis, angiogenesis and vascularization of tumour xenografts

  1999cited by this paper
• Each member of the Id gene family exhibits a unique expression pattern in mouse gastrulation and neurogenesis

  1997cited by this paper
• P-glycoprotein-mediated acquired multidrug resistance of human lung cancer cells in vivo.

  1996cited by this paper
• MyoD-induced expression of p21 inhibits cyclin-dependent kinase activity upon myocyte terminal differentiation

  1995cited by this paper
• Expression of Id2 and Id3 mRNA in human lymphocytes.

  1995cited by this paper
• The gene for the helix-loop-helix protein, Id, is specifically expressed in neural precursors.

  1992cited by this paper
• Heterodimers of myogenic helix-loop-helix regulatory factors and E12 bind a complex element governing myogenic induction of the avian cardiac alpha-actin promoter

  1991cited by this paper
• Long-term survival and toxicity in small cell lung cancer. Expanded Southwest Oncology Group experience.

  1991cited by this paper
• Cancer statistics

  1989cited by this paper

• A prevalent disease-associated SNP in the human ID3 gene regulates E-protein activity and cellular proliferation

  2026cites this paper
• Epigenetic Mechanisms in Neuroendocrine Neoplasms: Is There a Place for Inhibitors of DNA Binding Proteins?

  2025cites this paper
• Exploration of the optimal retention method in vivo for stem cell therapy: Low-intensity ultrasound preconditioning

  2025cites this paper
• TRIM21‐Mediated K11‐Linked Ubiquitination of ID1 Suppresses Tumorigenesis and Promotes Cuproptosis in Esophageal Squamous Cell Carcinoma

  2025cites this paper
• Integration of Metabolic Profiling and Functional Genomics Suggests IGJ as a Driver of Chemoresistance in B‐ALL

  2025cites this paper
• Functional Enrichment Analysis of Tumor Microenvironment–Driven Molecular Alterations That Facilitate Epithelial-to-Mesenchymal Transition and Distant Metastasis

  2024influential citation
• The therapeutic potential of RNA m(6)A in lung cancer

  2024cites this paper
• Engineered immunologic niche monitors checkpoint blockade response and probes mechanisms of resistance

  2024cites this paper
• Cleavage of semaphorin 4C interferes with the neuroprotective effect of the semaphorin 4C/Plexin B2 pathway on experimental intracerebral hemorrhage in rats.

  2023cites this paper
• Inhibition of angiogenesis using laminarin a natural polysaccharide from brown seaweeds – A review

  2023cites this paper
• Inhibitor of DNA binding/differentiation proteins as IDs for Pancreatic cancer: Role in pancreatic cancer initiation, development and prognosis.

  2022cites this paper
• Corticosterone triggers anti-proliferative and apoptotic effects, and downregulates the ACVR1-SMAD1-ID3 cascade in chicken ovarian prehierarchical, but not preovulatory granulosa cells.

  2022cites this paper
• Specific and Aspecific Molecular Checkpoints as Potential Targets for Dismantling Tumor Hierarchy and Preventing Relapse and Metastasis Through Shielded Cytolytic Treatments

  2021cites this paper
• ID1 mediates resistance to osimertinib in EGFR T790M-positive non-small cell lung cancer through epithelial–mesenchymal transition

  2021cites this paper
• The Adipokine Component in the Molecular Regulation of Cancer Cell Survival, Proliferation and Metastasis

  2021cites this paper
• Overexpression of ID1 mediates resistance to osimertinib in T790M positive non-small cell lung cancer through epithelial-mesenchymal transition

  2020cites this paper
• Comprehensive analysis of inhibitor of differentiation/DNA-binding gene family in lung cancer using bioinformatics methods

  2020cites this paper
• ID1 overexpression increases gefitinib sensitivity in non-small cell lung cancer by activating RIP3/MLKL-dependent necroptosis.

  2020cites this paper
• Inhibitor of Differentiation 1 (Id1) in Cancer and Cancer Therapy

  2020cites this paper
• Proteomic and transcriptomic profiling identifies mediators of anchorage-independent growth and roles of inhibitor of differentiation proteins in invasive lobular carcinoma

  2020cites this paper
• Notch Transduction in Non-Small Cell Lung Cancer

  2020cites this paper
• Combined treatment with CBP and BET inhibitors reverses inadvertent activation of detrimental super enhancer programs in DIPG cells

  2020cites this paper
• The inhibitor of DNA-binding family regulates the prognosis of ovarian cancer.

  2020cites this paper
• Similarities Between Embryo Development and Cancer Process Suggest New Strategies for Research and Therapy of Tumors: A New Point of View

  2019cites this paper
• Pancreatic cancer-initiating cell exosome message transfer into noncancer-initiating cells: the importance of CD44v6 in reprogramming

  2019cites this paper
• Las oposiciones a la organistía de la catedral de Salamanca en el siglo XVII. Estabilidad y dinámica

  2018cites this paper
• Id1 and Id3 synergistically influence invasion and migration of colon cancer SW620 cells by inducing EMT

  2018cites this paper
• Transcriptomic Predictors of Pulmonary Hypertension Development in Heart Failure Patients

  2018cites this paper
• Inhibitor of DNA binding proteins: implications in human cancer progression and metastasis.

  2018influential citation
• Letter to the Editor: Is Id3 proliferative or antiproliferative?

  2018cites this paper
• Thyroid Hormone Receptor SS (trß) Regulation Of Runt-Related Transcription Factor 2 (runx2) In Thyroid Tumorigenesis: Determination Of The Trß Nuclear Protein Complexes That Associate With The Runx2 Gene.

  2017cites this paper
• Effects of diabetes and Hoxa3 upon macrophage function

  2016cites this paper
• Upregulation of Id3 inhibits cell proliferation and induces apoptosis in A549/DDP human lung cancer cells in vitro.

  2016cites this paper
• Upregulation of Id 3 inhibits cell proliferation and induces apoptosis in A 549 / DDP human lung cancer cells in vitro

  2016cites this paper
• Effects of upregulation of Id3 in human lung adenocarcinoma cells on proliferation, apoptosis, mobility and tumorigenicity

  2015cites this paper
• The pleiotropic effects of fisetin and hesperetin on human acute promyelocytic leukemia cells are mediated through apoptosis, cell cycle arrest, and alterations in signaling networks

  2015cites this paper
• Therapeutic potentials of fisetin, hesperetin and vitexin on chronic myeloid leukemia and acute myeloid leukemia cells

  2015cites this paper
• of radioresistance in glioblastoma stem-like

  year unknowncites this paper