Related Experiment Video

Updated: May 24, 2025

Author Spotlight: Liujunzi Decoction as a Traditional Chinese Treatment for Coloproctitis Cancer
06:24

Author Spotlight: Liujunzi Decoction as a Traditional Chinese Treatment for Coloproctitis Cancer

Published on: October 13, 2023

784

TRIM38 Suppresses the Progression of Colorectal Cancer via Enhancing CCT6A Ubiquitination to Inhibit the MYC Pathway

Yue Zhang1,2,3,4, Xinyu Tan1,2,3,4, Lu Wang1,3,4

  • 1Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, 210029, P. R. China.

Advanced Science (Weinheim, Baden-Wurttemberg, Germany)
|March 6, 2025
PubMed

Insights

Tripartite motif protein 38 (TRIM38) acts as a tumor suppressor in colorectal cancer (CRC) by inhibiting cell growth and metastasis. Its downregulation, due to promoter hypermethylation, activates the MYC pathway, impacting CRC progression.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Colorectal cancer (CRC) is a major global health concern.
  • The role of tripartite motif protein (TRIM) family members in CRC is increasingly recognized.
  • The specific function and regulatory mechanisms of TRIM38 in CRC require further investigation.

Purpose of the Study:

  • To investigate the role of TRIM38 in colorectal cancer.
  • To elucidate the molecular mechanism underlying TRIM38's function in CRC.
  • To explore TRIM38 as a potential therapeutic target for CRC.

Main Methods:

  • Analysis of TRIM38 expression in CRC tissues.
  • Correlation of TRIM38 levels with clinical features and prognosis.
  • In vitro and in vivo experiments to assess TRIM38's tumor suppressor activity.
  • Identification of TRIM38 interacting proteins and ubiquitination targets.
  • Investigation of the TRIM38/CCT6A/c-Myc signaling axis.

Main Results:

  • TRIM38 is downregulated in CRC tissues due to promoter DNA hypermethylation.
  • Decreased TRIM38 expression correlates with adverse clinical outcomes and poor prognosis in CRC patients.
  • TRIM38 inhibits CRC cell proliferation, metastasis, and tumorigenesis.
  • TRIM38 targets CCT6A for K48-linked ubiquitination and degradation.
  • TRIM38 downregulation leads to CCT6A accumulation, c-Myc stabilization, and MYC pathway activation.

Conclusions:

  • TRIM38 functions as a tumor suppressor in colorectal cancer.
  • A novel TRIM38/CCT6A/c-Myc signaling pathway regulates CRC progression.
  • TRIM38, through its regulation of CCT6A and c-Myc, presents a potential therapeutic target for CRC.
Keywords:
CCT6AMYCTRIM38colorectal cancerubiquitination

More Related Videos

Development and Maintenance of a Preclinical Patient Derived Tumor Xenograft Model for the Investigation of Novel Anti-Cancer Therapies09:29

Development and Maintenance of a Preclinical Patient Derived Tumor Xenograft Model for the Investigation of Novel Anti-Cancer Therapies

Published on: September 30, 2016

13.6K
In vitro Organoid Culture of Primary Mouse Colon Tumors07:33

In vitro Organoid Culture of Primary Mouse Colon Tumors

Published on: May 17, 2013

35.0K

Related Concept Videos

Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
4.4K
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
3.7K
Loss of Tumor Suppressor Gene Functions01:12

Loss of Tumor Suppressor Gene Functions

Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
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...
4.7K
Inhibition of Cdk Activity02:34

Inhibition of Cdk Activity

The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
4.6K
Tumor Progression02:07

Tumor Progression

Tumor progression is a phenomenon where the pre-formed tumor acquires successive mutations to become clinically more aggressive and malignant. In the 1950s, Foulds first described the stepwise progression of cancer cells through successive stages.
Colon cancer is one of the best-documented examples of tumor progression. Early mutation in the APC gene in colon cells causes a small growth on the colon wall called a polyp. With time, this polyp grows into a benign, pre-cancerous tumor. Further...
6.2K
Cancer-Critical Genes II: Tumor Suppressor Genes01:05

Cancer-Critical Genes II: Tumor Suppressor Genes

Genes usually encode proteins necessary for the proper functioning of a healthy cell. Mutations can often cause changes to the gene expression pattern, thereby altering the phenotype.
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...
7.3K