CNDP1 Suppresses the Malignant Behavior of Hepatoma Cell via Restricting PI3K-AKT-mTOR Activation

Youwen Du1, Linxin Pan1, Wenchen Zhang1

  • 1School of Life Sciences, Anhui Medical University, Hefei, Anhui, China.

Current Cancer Drug Targets
|September 4, 2024
PubMed
Abstract

Insights

The enzyme CNDP1 is significantly decreased in hepatocellular carcinoma (HCC). Overexpressing CNDP1 suppresses HCC cell growth and migration, offering potential for gene therapy.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Hepatocellular carcinoma (HCC) presents a significant global health challenge with rising mortality.
  • Investigating gene-level mechanisms is crucial for advancing HCC diagnosis and treatment.
  • The role of CNDP1, an enzyme in carnosine hydrolysis, in HCC remains largely unexplored.

Purpose of the Study:

  • To investigate the role and mechanism of CNDP1 in hepatocellular carcinoma.
  • To identify CNDP1 as a potential therapeutic target for HCC.

Main Methods:

  • Bioinformatic analysis to screen differentially expressed genes in HCC.
  • Validation of CNDP1 expression in HCC tissues and cell lines.
  • Assessment of CNDP1's impact on hepatoma cell malignant behaviors (proliferation, migration, invasion) using various assays.
  • Exploration of the molecular mechanism involving the PI3K-AKT-mTOR pathway.

Main Results:

  • CNDP1 expression is significantly downregulated in HCC tissues and cell lines.
  • Overexpression of CNDP1 inhibits proliferation, migration, and invasion of HCC cells.
  • CNDP1 interacts with proteins in the PI3K-AKT-mTOR signaling pathway.
  • CNDP1 overexpression suppresses PI3K-AKT-mTOR pathway activation, and pathway inhibition counteracts CNDP1's anti-cancer effects.

Conclusions:

  • CNDP1 exhibits significant downregulation in HCC and possesses anti-cancer properties.
  • This study provides a foundation for understanding CNDP1's biological function in HCC.
  • CNDP1 presents potential as a diagnostic marker and therapeutic target for HCC gene therapy.

Related Concept Videos

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...
4.7K
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...
4.5K
PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a...
3.4K
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...
3.8K
Interactions Between Signaling Pathways01:19

Interactions Between Signaling Pathways

Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
6.2K
The JAK-STAT Signaling Pathway01:20

The JAK-STAT Signaling Pathway

Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as  SH2...
8.7K