February 9, 2017 The functions of Ror2 and IFT20 in invasive cancer cells. In healthy cells IFT20 regulates the formation and function of primary cilia. Many cancer cells lack cilia, and these cells induce and sustain the expression of IFT20 through the high expression of Ror2. IFT20 promotes the formation of Golgi-derived microtubules by binding with the GM130-AKAP450 complex in Golgi. By doing this it regulates the deployment of Golgi and transport of proteins within Golgi, both important parts of the formation of invadopodia. Credit: Kobe University

An international research team has discovered that the IFT20 protein helps some cancer cells to invade by facilitating the transportation of membranes and proteins within parts of the cell.

Primary cilia exist on the surface of almost all human cells, acting as "cell antenna" that receive information from outside the cell. IFT20 (intraflagellar transport 20) is a protein present in most human cells that plays an essential role in the formation and functions of these primary cilia. In healthy cells it acts as a "cargo adaptor" to transport proteins along microtubules within cilia, but many cells lose these cilia when they become cancerous. This research has shed light on the function of IFT20 in non-ciliated cancer cells for the first time. The discovery has potential applications for developing new cancer treatment methods that block invasive cancer cells by targeting IFT20. The findings were published on January 26 in the online edition of Scientific Reports.

This research was carried out by an international team including Associate Professor NISHITA Michiru (Kobe University Graduate School of Medicine Department of Physiology and Cell Biology), Professor MINAMI Yasuhiro (Kobe University Graduate School of Medicine, Department of Physiology and Cell Biology), Professor Victor W. Hsu (Harvard Medical School) and Professor Gregory J. Pazour (University of Massachusetts Medical School). Most cancer-related deaths are said to be caused by cell invasion and the consequent spread of cancer cells to other parts of the body (metastasis). To counter this, scientists are searching for the mechanism that controls the invasive properties of cancer cells.

Researchers already knew that a cell membrane protein known as Ror2 expresses highly in various cancer cells, and it promotes cancer cell invasion and metastasis. Professor Nishita's team investigated various kinds of non-ciliated cancer cells and discovered that Ror2 promoted cancer cell invasiveness by inducing the expression of IFT20.

Many tumor cells break through the barrier of the extracellular matrix and infiltrate their surroundings by forming protruding structures known as invadopodia (see figure). The formation of invadopodia requires membranes and proteins supplied by the intracellular transport system, using the Golgi complex. The Golgi complex must be close to invadopodia to deploy these materials. The team's findings demonstrate that in tumor cells, IFT20 induces the Golgi complex to form microtubules by promoting interaction between the Golgi proteins GM130 and AKAP450. It also regulates the structure of the Golgi complex and transport of proteins within the complex. "This research has clarified a new molecular mechanism related to the formation of Golgi-derived microtubules, and its important role in invasive cancer cells," said Professor Nishita.

The relationship between loss of cilia and a cell's cancerous properties remains unclear. IFT20 is involved in the formation and function of cilia in healthy cells, but in non-ciliated cancer cells it is now clear that IFT20 is responsible for the formation of invadopodia. By continuing to analyze the relationship between IFT20 and the loss of cilia, this line of research could help shed light on the fundamental question of why many cancer cells lack cilia. Additionally, if the specific regulatory mechanism of IFT20 in cancer cells is revealed, this knowledge could be used to develop treatment that targets IFT20 to block invasive cancer cells.

Explore further: Study reveals gene's role in male infertility

More information: Michiru Nishita et al, Ror2 signaling regulates Golgi structure and transport through IFT20 for tumor invasiveness, Scientific Reports (2017). DOI: 10.1038/s41598-016-0028-x

Journal reference: Scientific Reports

Provided by: Kobe University

A Virginia Commonwealth University-led research team has opened a fresh direction in the field of male infertility with a new study that examines the role of a particular gene in the formation of sperm flagella, which is ...

A cellular component known as the Golgi apparatus may play a role in how lung cancer metastasizes, according to researchers at The University of Texas MD Anderson Cancer Center whose findings were reported in the Nov. 21 ...

A family of proteins called G proteins are a recognized component of the communication system the human body uses to sense hormones and other chemicals in the bloodstream and to send messages to cells. In work that further ...

Scientists at the Universities of York and Texas have found that a component of cancer cells, which acts like a 'cellular post office', could be the key to preventing the spread of lung cancer to other parts of the body.

The research, conducted at Queen Mary University of London (QMUL), found that a slight regulation in the length of primary cilia, small hair-like projections found on most cells, prevented the production of fat cells from ...

(Medical Xpress)A team of researchers affiliated with multiple institutions in Korea has found that genetically altering a type of bacteria and injecting it into cancerous mice resulted in the disappearance of tumors in ...

A single blood test and basic information about a patient's medical status can indicate which patients with myelodysplastic syndrome (MDS) are likely to benefit from a stem cell transplant, and the intensity of pre-transplant ...

A paradigm-changing Ludwig Cancer Research study reveals that short fragments of circular DNA that encode cancer genes are far more common in cancer cells than previously believed and probably play a central role in generating ...

Studies abound that point to a role for plain old aspirin in keeping deadly cancers at bay. While aspirin is not yet part of mainstream treatment for any cancer, it is recommended by the U.S. Preventive Services Task Force ...

Cancerous tumors are voracious. Once they have consumed all the oxygen and nutrients in the original tumor site, the cancer cells travel to other parts of the body (metastasize) to find more nourishment.

A QUT-driven project has identified the way in which melanoma cells spread, opening up new pathways to treatment via drugs to 'turn off' the invasive gene.

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Follow this link:
IFT20 protein's role in helping cancer cells to invade - Medical Xpress