Nodal regulates bladder cancer cell migration and invasion via the ALK/Smad signaling pathway

Youkong Li1, Wen Zhong2, Min Zhu1

  • 1Department of Urology, Jingzhou Central Hospital and The Second Clinical Medical College, Yangtze University, Jingzhou 434020, People's Republic of China, yiukongli0412@163.com.

Oncotargets and Therapy
|October 17, 2018
PubMed
Abstract

Insights

Nodal acts as an oncogene in bladder cancer, promoting cell proliferation and invasion. Inhibiting Nodal may offer a new treatment strategy for bladder cancer by targeting the ALK/Smad signaling pathway.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Biology

Background:

  • Bladder cancer is a prevalent urinary tract malignancy.
  • The role and mechanisms of Nodal in bladder cancer remain largely unexplored.

Purpose of the Study:

  • To investigate the biological function of Nodal in bladder cancer.
  • To elucidate the molecular mechanisms underlying Nodal's role in bladder cancer progression.

Main Methods:

  • Quantitative real-time PCR to assess Nodal expression in tissues and cells.
  • In vitro assays (MTT, colony formation, transwell) to evaluate Nodal's impact on cell proliferation, migration, and invasion.
  • Western blot to analyze protein expression related to proliferation, invasion, and the ALK/Smad signaling pathway.

Main Results:

  • Nodal expression is significantly upregulated in bladder cancer.
  • Nodal downregulation inhibits bladder cancer cell proliferation, clone formation, migration, and invasion.
  • Nodal affects the expression of key proteins (CDC6, E-cadherin, MMP-2, MMP-9) and components of the ALK/Smad pathway (ALK4, ALK7, Smad2, Smad4).
  • SB431542, an ALK4/7 inhibitor, reverses Nodal-induced pro-tumorigenic effects.

Conclusions:

  • Nodal functions as an oncogene in bladder cancer.
  • Nodal promotes bladder cancer progression by regulating proliferation, migration, and invasion through the ALK/Smad signaling pathway.
  • Targeting Nodal and the ALK/Smad pathway presents a potential therapeutic strategy for bladder cancer.

Related Concept Videos

Cancer Cell Migration through Invadopodia01:35

Cancer Cell Migration through Invadopodia

Invadosome is a broad category of cell surface structures with proteolytic activity that  degrades the extracellular matrix (ECM). Invadosomes are present in normal cell types, including macrophages, endothelial cells, and neurons, as well as tumor cells. Although the macrophage podosomes and tumor cell invadopodia are classified as invadosomes, they have different structures, molecular pathways, and functions. Podosomes are short structures that last for a few minutes. However,...
3.3K
Notch Signaling Pathway03:14

Notch Signaling Pathway

The Notch signaling pathway is a major intracellular signaling pathway that is highly conserved over a broad spectrum of metazoan species. It stands unique from other intracellular signaling mechanisms in animals because notch protein itself acts as the receptor as well as the primary signaling molecule.
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not...
6.6K
Hedgehog Signaling Pathway02:33

Hedgehog Signaling Pathway

The Hedgehog gene (Hh) was first discovered due to its control of the growth of disorganized, hair-like bristles phenotype in Drosophila, much like hedgehog spines. Hh plays a crucial role in the development of organs and the maintenance of homeostasis in both invertebrates and vertebrates. However, while Drosophila has only one Hh protein, mammals have multiple functional Hedgehog proteins - Sonic (Shh), Desert (Dhh), and Indian Hedgehog (Ihh). All of these homologous proteins have adapted to...
10.1K
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...
7.4K
Nodal Analysis01:10

Nodal Analysis

Nodal analysis is a fundamental method in electrical engineering used to simplify the process of circuit analysis. This method revolves around the concept of using node voltages as the primary variables for circuit analysis. The objective is to determine the voltage at each node in a circuit, which can then be used to find other quantities of interest, such as currents through specific components.
Consider, for instance, a simple circuit composed of three nodes and three resistors, as shown in...
1.9K
Non-Canonical Wnt Signaling Pathways01:41

Non-Canonical Wnt Signaling Pathways

Wnt is a zygotic effect gene that is expressed during very early embryonic development. It regulates various processes in animals starting from early development through the adult stage, such as organogenesis in the embryo and maintenance of neuronal and blood stem cells. Wnt proteins can induce a wide variety of intracellular pathways depending upon the specific abilities of different Wnt ligands to form a complex with shared and cognate receptors in the presence of different co-receptors. The...
8.5K