DTL promotes the growth and migration of melanoma cells through the ERK/E2F1/BUB1 axis

Xiuyun Xuan1, Juanmei Cao1,2, Li Chen3

  • 1Department of Dermatology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, Hubei, China.

Scientific Reports
|November 2, 2024
PubMed

Insights

The DTL gene drives melanoma progression by promoting cell proliferation, invasion, and migration through the ERK/E2F1/BUB1 pathway. Targeting DTL offers a potential therapeutic strategy for melanoma patients.

Area of Science:

  • Oncology
  • Molecular Biology
  • Dermatology

Background:

  • Melanoma is a dangerous skin cancer requiring better understanding of its pathogenesis.
  • Identifying novel molecular targets is crucial for advancing melanoma therapy.

Purpose of the Study:

  • To investigate the role of the DTL gene in melanoma pathogenesis.
  • To elucidate the molecular mechanisms underlying DTL's function in melanoma.

Main Methods:

  • Integrated bioinformatics analysis to screen for relevant genes.
  • Validation of DTL expression in melanoma tissues and cells.
  • In vitro experiments assessing cell behavior (proliferation, invasion, migration, EMT) with DTL manipulation.
  • In vivo studies to evaluate DTL's effect on melanoma malignancy.
  • Mechanistic studies involving downstream targets (BUB1, ERK, E2F1) and rescue experiments.

Main Results:

  • DTL gene expression is upregulated in melanoma and associated with increased proliferation, invasion, migration, and EMT.
  • DTL knockdown suppresses melanoma cell malignancy both in vitro and in vivo.
  • BUB1 is a key downstream target of DTL, mediating its effects on cell growth and migration.
  • DTL regulates the ERK/E2F1/BUB1 signaling axis, which is critical for melanoma cell behavior.

Conclusions:

  • DTL promotes melanoma malignancy via the ERK/E2F1/BUB1 pathway.
  • DTL represents a potential prognostic marker and therapeutic target for melanoma.

Related Concept Videos

Mitogens and the Cell Cycle02:38

Mitogens and the Cell Cycle

Mitogens and their receptors play a crucial role in controlling the progression of the cell cycle. However, the loss of mitogenic control over cell division leads to tumor formation. Therefore, mitogens and mitogen receptors play an important role in cancer research. For instance, the epidermal growth factor (EGF) - a type of mitogen and its transmembrane receptor (EGFR), decides the fate of the cell's proliferation. When EGF binds to EGFR, a member of the ErbB family of tyrosine kinase...
6.4K
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
MAPK Signaling Cascades01:07

MAPK Signaling Cascades

Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
5.2K
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
TGF - β Signaling Pathway01:16

TGF - β Signaling Pathway

The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors...
7.2K