Related Experiment Video
Updated: Jul 5, 2026
HOX Loci Focused CRISPR/sgRNA Library Screening Identifying Critical CTCF Boundaries
Published on: March 31, 2019
The E3 ligase HACE1 is a critical chromosome 6q21 tumor suppressor involved in multiple cancers
Liyong Zhang1, Michael S Anglesio, Maureen O'Sullivan
1Institute of Molecular Biotechnology of the Austrian Academy of Sciences, Dr. Bohrgasse 3, 1030 Vienna, Austria.
Abstract:
Transformation and cancer growth are regulated by the coordinate actions of oncogenes and tumor suppressors. Here, we show that the novel E3 ubiquitin ligase HACE1 is frequently downregulated in human tumors and maps to a region of chromosome 6q21 implicated in multiple human cancers. Genetic inactivation of HACE1 in mice results in the development of spontaneous, late-onset cancer. A second hit from either environmental triggers or genetic heterozygosity of another tumor suppressor, p53, markedly increased tumor incidence in a Hace1-deficient background. Re-expression of HACE1 in human tumor cells directly abrogates in vitro and in vivo tumor growth, whereas downregulation of HACE1 via siRNA allows non-tumorigenic human cells to form tumors in vivo. Mechanistically, the tumor-suppressor function of HACE1 is dependent on its E3 ligase activity and HACE1 controls adhesion-dependent growth and cell cycle progression during cell stress through degradation of cyclin D1. Thus, HACE1 is a candidate chromosome 6q21 tumor-suppressor gene involved in multiple cancers.
Insights
The novel E3 ubiquitin ligase HACE1 is frequently downregulated in human tumors. Loss of HACE1 function in mice leads to spontaneous cancer, identifying it as a crucial tumor suppressor gene.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Cancer development is regulated by oncogenes and tumor suppressors.
- The E3 ubiquitin ligase HACE1 is a novel gene frequently downregulated in human tumors.
- HACE1 is located on chromosome 6q21, a region implicated in various human cancers.
Purpose of the Study:
- To investigate the role of HACE1 as a tumor suppressor gene.
- To elucidate the mechanism by which HACE1 regulates cancer growth.
Main Methods:
- Genetic inactivation of HACE1 in mice.
- Analysis of HACE1 expression in human tumors.
- Re-expression of HACE1 in human tumor cells.
- siRNA-mediated downregulation of HACE1.
- Assessment of tumor growth in vitro and in vivo.
- Investigation of HACE1's effect on cell cycle progression and cyclin D1 degradation.
Main Results:
- HACE1 is frequently downregulated in human tumors and maps to chromosome 6q21.
- Genetic inactivation of HACE1 in mice leads to spontaneous, late-onset cancer.
- Loss of HACE1 accelerates tumor development, especially with a second hit (p53 heterozygosity or environmental triggers).
- Re-expression of HACE1 inhibits tumor growth, while HACE1 downregulation promotes tumorigenesis.
- HACE1's tumor-suppressive function relies on its E3 ligase activity, controlling adhesion-dependent growth and cell cycle via cyclin D1 degradation.
Conclusions:
- HACE1 is a novel tumor suppressor gene involved in multiple cancers.
- HACE1's E3 ligase activity is critical for its tumor-suppressive function.
- HACE1 regulates cell cycle progression and adhesion-dependent growth by degrading cyclin D1.
Related Concept Videos
02:23Abnormal Proliferation
01:33Cancer-Critical Genes I: Proto-oncogenes
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
01:12Loss of Tumor Suppressor Gene Functions
When the tumor suppressor genes develop mutations or are lost, cells start growing out of control, leading to cancer. However, a single functional copy of the tumor suppressor gene is enough for the cells to maintain their normal functions and cell...
01:05Cancer-Critical Genes II: Tumor Suppressor Genes
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
01:05Cancer-Critical Genes II: Tumor Suppressor Genes
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
01:12Loss of Tumor Suppressor Gene Functions
When the tumor suppressor genes develop mutations or are lost, cells start growing out of control, leading to cancer. However, a single functional copy of the tumor suppressor gene is enough for the cells to maintain their normal functions and cell...