Thousands of tiny anchor points keep our cells in place. How is this done?

Most of the cells in our body—whether they are bone cells, muscle cells, or pancreatic cells—are locked in the right place with the help of tiny anchors (called "local adhesions")

These "anchors" help the cells stay in place and in most cases resist damage from the external environment-but if a cell mutates into a cancer cell, the "anchor" chain will break, allowing the cancer cell to spread to other parts of the body

Now, a group of scientists at the University of New South Wales in Sydney have discovered the protein chain (or link) that maintains this connection for the first time

These findings, published today in the journal Nature Materials, are based on our understanding of cell mechanics and may help provide new directions for cancer research

The lead author of the study, Ms.

"If these attachments fail, cells may be more likely to move and invade tissues, such as cancer

Scientists already know that cancer weakens the anchor of the cell in some way, but they don't know how this happens

One of the reasons why research is so difficult is the tiny size of the anchor chain: it is only a few nanometers thick-about one ten thousandth of a human hair

The team used a specialized 3D cryo-electron microscope—a powerful imaging technique that uses electron microscopy to create high-resolution images of cells—to identify tropomyosin as a key protein in the anchor chain

"This is the first time we have really seen the details of the anchor chain," said Professor Peter Ganning, the co-senior author of the study

"This is a brand new technology

The researchers determined the role of tropomyosin in the anchor chain by comparing normal cells, cells from patients with bone cancer, and cancer cells produced in the laboratory

Then they tried to put tropomyosin back into the cancer cells-surprisingly, the anchors successfully attached to the cancer cells again

Ms.

"In the short term, we can use this information to determine whether the cancer has a tendency to metastasize

"In the long run, we can use it as a potential target for cancer treatment

Professor Gunning and Professor Edna Hardeman, a senior author who has been researching this scientific field for 40 years, said that this is a milestone in understanding cell mechanics
.

Professor Gunning recently received the 2020 Presidential Medal from the Australian and New Zealand Society for Cell and Developmental Biology (ANZSCDB) in recognition of his contributions to cell mechanics research
.

"It reinforces our life's work: understanding the principles of cell structure
.
"

A potential drug target

About 30% of the body is composed of collagen, which forms the so-called "matrix"
.

"The matrix is ​​like a scaffold that exists in our bones, ligaments, muscles, and skin
.
It's almost everywhere," Ms.
Lastra Cargas said
.
"Except for those cells that move in our body, such as those in the blood, the collagen matrix constitutes the home of most cells, including cancer cells
.
"

Pancreatic cancer is one of the few cancers that can change this matrix by creating a "barrier" around the tumor
.
This barrier acts as a defense mechanism, making it more difficult for cancer treatments such as chemotherapy and immunotherapy to kill cancer cells
.

The tumor forces pancreatic cancer-associated fibroblasts (or PCAFs)-cells fixed by chains around the tumor-to build this defense barrier
.
But now that scientists have identified the proteins in the cell anchors and chains, they can explore these proteins as future therapeutic targets, which may relax this barrier
.

Professor Hardman said: "We have determined that the tropomyosin involved in this chain is medicinal
.
"

"This means that it is possible to develop small molecule inhibitors or drugs that can attack these proteins
.
"

Professor Hardman said that these potential future drugs are likely to be used in conjunction with cancer treatments, so these drugs can temporarily disrupt the barrier while cancer treatments are working
.

Look to the future

Professor Gan Ning said that although these findings are encouraging, they do not mean that suitable drugs will be available in the next few years
.

He said: "We have some understanding of biology, but it is difficult to predict from biology to treatment of patients
.
"

"We can see the future development path, but we are not sure about the specific time
.
"

More likely, in the near future—probably in the next two or three years—the tropomyosin in the gene chain may help scientists predict which cancers may spread faster
.

Professor Gan Ning said: "When we build on the underlying mechanisms of cancer and expand our biological markers of cancer cells, our discovery adds a missing link to the development of personalized cancer diagnosis
.
"

DOI

10.
1038 / s41563-021-01087-z

Correlative cryo-ET identifies actin/tropomyosin filaments that mediate cell–substrate adhesion in cancer cells and mechanosensitivity of cell proliferation