Silencing Delta-like 1 Expression Induces Migratory Features in Pancreatic Cancer Cells Through Stimulation of Src

Jungwhoi Lee1, Jungsul Lee2, DA Hye Kim3

  • 1Department of Applied Life Science, SARI, Jeju National University, Jeju-do, Republic of Korea sdjd1108@kaist.ac.kr kimjh@jejunu.ac.kr.

Anticancer Research
|March 6, 2020
PubMed
Abstract

Insights

Delta-like 1 (DLL1) suppresses pancreatic cancer metastasis by inhibiting cell migration and invasion. High DLL1 expression correlates with a better prognosis in pancreatic cancer patients.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • Pancreatic cancer prognosis remains poor due to metastasis and chemo-resistance, with unclear underlying mechanisms.
  • Delta-like 1 (DLL1) is investigated for its role in the metastatic potential of human pancreatic cancer cells.

Purpose of the Study:

  • To investigate the function of delta-like 1 (DLL1) as a tumor suppressor in human pancreatic cancer cell metastasis.

Main Methods:

  • Analyzed DLL1 expression using GEO public database and western blot.
  • Validated DLL1's biological function through cell behavior analysis.
  • Correlated DLL1 expression with patient prognosis using the GEO public database.

Main Results:

  • DLL1 mRNA and protein were upregulated in pancreatic cancer tissues and cell lines.
  • DLL1 ablation enhanced migration and invasion by activating Src and p38 phosphorylation.
  • DLL1 expression correlated with reduced in vivo metastasis and a favorable patient prognosis.

Conclusions:

  • DLL1 acts as a potent suppressor of pancreatic cancer metastasis.
  • Understanding DLL1's expression-function correlation advances knowledge of pancreatic cancer metastasis mechanisms.

Related Concept Videos

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...
7.1K
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...
7.7K
Role Of Notch Signalling In Intestinal Stem Cell Renewal01:12

Role Of Notch Signalling In Intestinal Stem Cell Renewal

Notch signaling was first discovered in Drosophila melanogaster, where it is involved in cell lineage differentiation. Notch signaling regulates the maintenance and differentiation of intestinal stem cells or ISCs by controlling the expression of atonal homolog 1 or Atoh1. Atoh1 directs cells to differentiate into secretory cells.
Direct cell-to-cell contact is needed for the activation of Notch signaling. The signal is initiated when a notch ligand binds to a receptor on an adjacent cell, also...
2.4K
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...
11.6K
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...
4.5K