Nav: Home

It's what's inside that matters: Locking up proteins enables cancer metastasis

March 03, 2020

Researchers from Tokyo Medical and Dental University (TMDU) discover a novel mechanism by which claudin-1 contributes to the progression of tongue squamous cell carcinoma

Tokyo, Japan - While it is known that most cancers try to grow and spread to the rest of the body, for many cancers it is unclear how they actually achieve taking over the host's body. In a new study published in Cancer Science, researchers from Tokyo Medical and Dental University (TMDU) revealed a novel mechanism by which tongue squamous cell carcinoma (TSCC) exploits a protein whose task actually is to keep the tissue together.

A group of cells, also called tissue, is held together by a number of proteins that form a complex called tight junctions on the cell surface. Their function is to provide stability to the tissue as well as to prevent leakage of transported solutes and water by ensuring that molecules only pass through, and not between, the cells. One of the proteins that is part of tight junctions is claudin-1. Several studies have shown that claudin-1 plays an important role in several cancers, such as oral, gastric, liver and colon cancer.

"The amount of claudin-1 that a cancer makes has not been shown to correlate with how malignant that cancer is," says corresponding author of the study Miki Hara-Yokoyama. "The goal of our study was to understand at the molecular level how claudin-1 is involved in cancer progression."

To achieve their goal, the researchers investigated specimens from patients with TSCC for the amount of claudin-1 produced by the cancer, as well as where in the cancer cell the protein is located. Given that claudin-1 is part of tight junctions, one might expect that they are naturally localized to the cell surface. It turns out it is not that simple.

"We know that localization is a key determinant of protein function. So we wanted to know if the localization of claudin-1 was connected to the progression of TSCC," says lead author of the study Daisuke Yamamoto.

The researchers found that although the total amount of claudin-1 in TSCC cells and the invasiveness of the cancer were not associated, the amount of claudin-1 localized to the interior of the cell increased with the degree of cervical lymph node metastasis. They then isolated cells from TSCC and showed that when claudin-1 is locked within the cells or when the cells are entirely depleted of claudin-1, the cancer cells become more migratory.

"These are striking results that show how cancer cells break free from a tissue and increase their motility to invade lymph nodes and other organs of the body," says Hara-Yokoyama. "Invasive cancers that are capable of spreading and disabling vital organ functions are often very difficult to contain. Our findings could offer a novel therapy to prevent cancers from progressing and metastasizing."
The article, "Intracellular claudin-1 at the invasive front of tongue squamous cell carcinoma is associated with lymph node metastasis," was published in Cancer Science at DOI: 10.1111/cas.14249

Tokyo Medical and Dental University

Related Cancer Articles:

Cancer mortality continues steady decline, driven by progress against lung cancer
The cancer death rate declined by 29% from 1991 to 2017, including a 2.2% drop from 2016 to 2017, the largest single-year drop in cancer mortality ever reported.
Stress in cervical cancer patients associated with higher risk of cancer-specific mortality
Psychological stress was associated with a higher risk of cancer-specific mortality in women diagnosed with cervical cancer.
Cancer-sniffing dogs 97% accurate in identifying lung cancer, according to study in JAOA
The next step will be to further fractionate the samples based on chemical and physical properties, presenting them back to the dogs until the specific biomarkers for each cancer are identified.
Moffitt Cancer Center researchers identify one way T cell function may fail in cancer
Moffitt Cancer Center researchers have discovered a mechanism by which one type of immune cell, CD8+ T cells, can become dysfunctional, impeding its ability to seek and kill cancer cells.
More cancer survivors, fewer cancer specialists point to challenge in meeting care needs
An aging population, a growing number of cancer survivors, and a projected shortage of cancer care providers will result in a challenge in delivering the care for cancer survivors in the United States if systemic changes are not made.
New cancer vaccine platform a potential tool for efficacious targeted cancer therapy
Researchers at the University of Helsinki have discovered a solution in the form of a cancer vaccine platform for improving the efficacy of oncolytic viruses used in cancer treatment.
American Cancer Society outlines blueprint for cancer control in the 21st century
The American Cancer Society is outlining its vision for cancer control in the decades ahead in a series of articles that forms the basis of a national cancer control plan.
Oncotarget: Cancer pioneer employs physics to approach cancer in last research article
In the cover article of Tuesday's issue of Oncotarget, James Frost, MD, PhD, Kenneth Pienta, MD, and the late Donald Coffey, Ph.D., use a theory of physical and biophysical symmetry to derive a new conceptualization of cancer.
Health indicators for newborns of breast cancer survivors may vary by cancer type
In a study published in the International Journal of Cancer, researchers from the UNC Lineberger Comprehensive Cancer Center analyzed health indicators for children born to young breast cancer survivors in North Carolina.
Few women with history of breast cancer and ovarian cancer take a recommended genetic test
More than 80 percent of women living with a history of breast or ovarian cancer at high-risk of having a gene mutation have never taken the test that can detect it.
More Cancer News and Cancer Current Events

Trending Science News

Current Coronavirus (COVID-19) News

Top Science Podcasts

We have hand picked the top science podcasts of 2020.
Now Playing: TED Radio Hour

Climate Mindset
In the past few months, human beings have come together to fight a global threat. This hour, TED speakers explore how our response can be the catalyst to fight another global crisis: climate change. Guests include political strategist Tom Rivett-Carnac, diplomat Christiana Figueres, climate justice activist Xiye Bastida, and writer, illustrator, and artist Oliver Jeffers.
Now Playing: Science for the People

#562 Superbug to Bedside
By now we're all good and scared about antibiotic resistance, one of the many things coming to get us all. But there's good news, sort of. News antibiotics are coming out! How do they get tested? What does that kind of a trial look like and how does it happen? Host Bethany Brookeshire talks with Matt McCarthy, author of "Superbugs: The Race to Stop an Epidemic", about the ins and outs of testing a new antibiotic in the hospital.
Now Playing: Radiolab

Speedy Beet
There are few musical moments more well-worn than the first four notes of Beethoven's Fifth Symphony. But in this short, we find out that Beethoven might have made a last-ditch effort to keep his music from ever feeling familiar, to keep pushing his listeners to a kind of psychological limit. Big thanks to our Brooklyn Philharmonic musicians: Deborah Buck and Suzy Perelman on violin, Arash Amini on cello, and Ah Ling Neu on viola. And check out The First Four Notes, Matthew Guerrieri's book on Beethoven's Fifth. Support Radiolab today at