Ror2 signaling regulates Golgi structure and transport through IFT20 for tumor invasiveness

Michiru Nishita1, Seung-Yeol Park2, Tadashi Nishio3

  • 1Division of Cell Physiology, Department of Physiology and Cell Biology, Kobe University, Graduate School of Medicine, Kobe, 650-0017, Japan. nishita@med.kobe-u.ac.jp.

Scientific Reports
|January 28, 2017
PubMed

Insights

Intraflagellar transport 20 (IFT20) is a new target of Ror2 signaling in tumors. IFT20 promotes tumor invasion by regulating Golgi structure and transport, offering new therapeutic targets.

Area of Science:

  • Cell Biology
  • Cancer Research
  • Molecular Biology

Background:

  • Ror2 receptor tyrosine kinase signaling drives invadopodia formation and tumor invasion.
  • The role of Ror2 signaling in tumors lacking primary cilia is not fully understood.

Purpose of the Study:

  • To identify novel targets of Ror2 signaling in tumor invasion.
  • To elucidate the mechanism by which Ror2 signaling promotes tumor invasiveness in non-ciliated tumors.

Main Methods:

  • Investigated the interaction between Ror2 signaling and intraflagellar transport 20 (IFT20).
  • Examined the regulation of Golgi-derived microtubules and Golgi ribbon formation by IFT20.
  • Assessed the impact of IFT20 on Golgi transport efficiency and tumor cell invasion.

Main Results:

  • IFT20 was identified as a novel target of Ror2 signaling in tumors lacking primary cilia.
  • IFT20 mediates Ror2-induced tumor invasiveness by regulating Golgi-derived microtubule nucleation via the GM130-AKAP450 complex.
  • IFT20 promotes Golgi ribbon formation, polarized secretion, and enhances Golgi transport efficiency.

Conclusions:

  • Ror2 signaling promotes tumor invasiveness through IFT20, which regulates Golgi structure and transport.
  • IFT20 represents a key mediator in Ror2-driven tumor cell migration and invasion.
  • These findings provide new insights into Ror2 signaling pathways and Golgi complex regulation in cancer.

Related Concept Videos

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...
5.0K
Intracellular Signaling Affects Focal Adhesions01:17

Intracellular Signaling Affects Focal Adhesions

Integrins act both as extracellular input receivers and as intracellular processing activators. As their name suggests, integrins are entirely integrated into the membrane structure. Their hydrophobic membrane-spanning regions interact with the phospholipid bilayer's hydrophobic region. These membrane receptors provide extracellular attachment sites for effectors like hormones and growth factors. They activate intracellular response cascades when their effectors are bound and active.
Some...
3.7K
Microtubules in Signaling01:22

Microtubules in Signaling

The primary cilium, made up of microtubules, acts as antennae on the cell surfaces for relaying external stimuli into the cells. These fine hair-like structures are present, generally one per cell. These are non-motile cilia in a 9+0 microtubules arrangement, where the central pair of microtubules are absent. The primary cilia arise from the basal body embedded in the cell membrane. Intraflagellar transport (IFT) carries requisite proteins from the cytoplasm to the cilium because the primary...
2.2K
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...
6.1K
Intracellular Signaling Cascades01:24

Intracellular Signaling Cascades

Once a ligand binds to a receptor, the signal is transmitted through the membrane and into the cytoplasm. The continuation of a signal in this manner is called signal transduction. Signal transduction only occurs with cell-surface receptors, which cannot interact with most components of the cell, such as DNA. Only internal receptors can interact directly with DNA in the nucleus to initiate protein synthesis. When a ligand binds to its receptor, conformational changes occur that affect the...
54.2K
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...
10.8K