TRIB2 functions as novel oncogene in colorectal cancer by blocking cellular senescence through AP4/p21 signaling

Zhenlin Hou1, Kaixuan Guo1, Xuling Sun1

  • 1Cancer Research Institute, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, China.

Molecular Cancer
|December 14, 2018
PubMed
Abstract

Insights

Tribbles homolog 2 (TRIB2) suppresses cellular senescence in colorectal cancer (CRC) by inhibiting p21 expression via AP4 interaction. Targeting TRIB2 may offer a new therapeutic strategy for CRC patients.

Area of Science:

  • Oncology
  • Cell Biology
  • Molecular Mechanisms

Background:

  • Cellular senescence is a key mechanism for tumor suppression.
  • Tribbles homolog 2 (TRIB2) influences cancer cell proliferation and drug resistance.
  • The role of TRIB2 in colorectal cancer (CRC) senescence and its underlying mechanisms are not well understood.

Purpose of the Study:

  • To investigate the role of TRIB2 in cellular senescence of colorectal cancer.
  • To elucidate the molecular mechanism by which TRIB2 regulates senescence in CRC.
  • To evaluate TRIB2 as a potential therapeutic target for CRC.

Main Methods:

  • Immunohistochemistry and RT-PCR to assess TRIB2 expression in CRC tissues.
  • Cell Counting Kit-8, flow cytometry, and senescence-associated β-galactosidase staining to evaluate cellular senescence.
  • Western blot, RT-PCR, luciferase assay, immunoprecipitation, and chromatin-immunoprecipitation to determine TRIB2's regulatory mechanism on p21 and AP4 interaction.

Main Results:

  • TRIB2 expression is upregulated in CRC tissues and correlates with poor prognosis.
  • TRIB2 depletion inhibits CRC cell proliferation and induces senescence, while TRIB2 overexpression promotes proliferation and blocks senescence.
  • TRIB2 interacts with AP4, inhibiting p21 expression and consequently suppressing cellular senescence.

Conclusions:

  • TRIB2 suppresses cellular senescence in CRC by interacting with AP4 to downregulate p21 expression.
  • TRIB2 represents a potential therapeutic target for colorectal cancer treatment.

Related Concept Videos

Cancer-Critical Genes I: Proto-oncogenes01:33

Cancer-Critical Genes I: Proto-oncogenes

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...
11.5K
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...
4.8K
Replicative Cell Senescence02:15

Replicative Cell Senescence

Replicative cell senescence is a property of cells that allows them to divide a finite number of times throughout the organism's lifespan while preventing excessive proliferation. Replicative senescence is associated with the gradual loss of the telomere — short, repetitive DNA sequences found at the end of the chromosomes. Telomeres are bound by a group of proteins to form a protective cap on the ends of chromosomes. Embryonic stem cells express telomerase — an enzyme that adds...
4.4K
Endocrine Signaling01:45

Endocrine Signaling

Endocrine cells produce hormones to communicate with remote target cells found in other organs. The hormone reaches these distant areas using the circulatory system. This exposes the whole organism to the hormone but only those cells expressing hormone receptors or target cells are affected. Thus, endocrine signaling induces slow responses from its target cells but these effects also last longer.
68.1K
Block Diagram Reduction01:22

Block Diagram Reduction

The process of deriving the transfer function of a control system often involves reducing its block diagram to a single block. This simplification can be achieved through a series of strategic operations, including relocating branch points and comparators. These operations preserve the overall function of the system while allowing for easier manipulation and combination of blocks.
The first step in this process is the identification and relocation of a branch point. A branch point, where a...
559
Elements of Block Diagrams01:25

Elements of Block Diagrams

Block diagrams serve as a visual representation of the input-output relationships within a system. An illustrative example is a heating system, where the set temperature activates the furnace to warm the room to the desired level. Block diagrams are versatile, modeling linear systems through Laplace transform variables and nonlinear systems using time domain variables.
A block diagram typically includes essential elements such as comparators, blocks, and feedback loops. Each of these elements...
701