Researchers Identify Protein that Makes Skin Cancer Cells More Invasive

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Squamous cell carcinoma of a human, photomicrograph panorama as seen under the microscope, 200x zoom.

Squamous cell carcinoma is a common type of skin cancer, usually affecting skin that is exposed to the damaging ultraviolet rays of the sun.

Researchers have found that the loss of a protein that normally helps repair DNA called
Tripartite Motif-Containing Protein 29 (TRIM29) promotes cancer cell invasion in a common type of skin cancer. Based on their results, they believe that this may suggest a novel diagnostic marker and a possible therapeutic target.

Proteins of the TRIM family have been implicated in breast, pancreas, prostate, lungs, bladder and stomach cancer. However, the role of this protein in squamous cell carcinoma was, until now, unknown.


…TRIM29 could be a novel diagnostic and prognostic marker in squamous cell cancers common in skin, neck and head…


A research team led by dermatologist Teruki Yanagi and Professor Shigetsugu Hatakeyama at Hokkaido University investigated cutaneous head and neck squamous cell carcinomas (SCC) and its functions in the tumorigenesis of such cancers and found that human squamous carcinoma cells with lower levels of TRIM29 were more mobile and invasive. This, in turn, correlated with a worse prognosis.

Photo 1.0: TRIM29 knockdown increases the metastatic potential of human squamous cell carcinoma (SCC). SCC cells were injected to mice with (right) or without (left) knocking down TRIM29 gene. Images were taken 23 days after the injection.

This study was published in Cancer Research, published by the American Association for Cancer Research (AACR)

TRIM29 expression was highest in normal skin cells. It was lower in squamous cell carcinomas, and even lower in tumors that metastasized, migrating from the main cancer site to other parts of the body, such as the lungs. The researchers also determined that turning off the gene made the cancer cells more mobile and invasive, both in cell cultures and mice.

Interestingly, they found that TRIM29 interacts with another protein inside cells called keratin, which plays numerous roles in forming a protective structural framework within cells and also in cell motility and signalling.

When TRIM29 levels are normal in a cell, it makes sure keratin is widely distributed within the cytoplasm. On the other hand, when TRIM29 levels are low, keratin distributes mainly around the cell nucleus, resulting in altered cell shapes.

Photo 2.0: TRIM29 knockdown (right) led to the perinuclear distribution of keratin in human squamous cell carcinoma cells. The left panel shows the control experiment. White: Keratin.

Novel diagnostic and prognostic marker
Previous studies had shown that TRIM29 suppressed breast and prostate cancer development, because the protein is spread throughout the cytoplasm in these types of cells. But it promoted development of pancreatic, lung, bladder and stomach cancers, where it is localized in the nucleus. In skin cells, TRIM29 is normally positioned throughout the cytoplasm, reinforcing its protective role in suppressing skin cancer.

“Our findings suggest that TRIM29 could be a novel diagnostic and prognostic marker in squamous cell cancers common in skin, neck and head. The TRIM-29/keratin interaction could also be a therapeutic target for treating advanced and metastatic squamous cell cancers,” Teruki Yanagi said.

The study was funded by the Japanese Ministry of Education, Culture, Sports, Science, and Technology, Ichiro Kanehara Foundation for the Promotion of Medical Science, Cosmetology Research Foundation, Ono Cancer Research Foundation, Takeda Science Foundation.

Reference
Yanagi T, Watanabe M, Hata H, Kitamura S, Imafuku K, Yanagi H, Homma A, et al.
Loss of TRIM29 alters keratin distribution to promote cell invasion in squamous cell carcinoma. Cancer Res. 2018 Nov 2. pii: canres.1495.2018. doi: 10.1158/0008-5472.CAN-18-1495. [Pubmed][Article]


Last Editorial Review: November 22, 2018

Featured Image: Squamous cell carcinoma of a human, photomicrograph panorama as seen under the microscope, 200x zoom. Courtesy: 2018 © Fotolia. Used with permission. Photo 1.0: TRIM29 knockdown increases the metastatic potential of human squamous cell carcinoma (SCC). SCC cells were injected to mice with (right) or without (left) knocking down TRIM29 gene. Images were taken 23 days after the injection. Courtesy: 2018 © Yanagi T. et al., Cancer Research, November 2, 2018. Photo 2.0: TRIM29 knockdown (right) led to the perinuclear distribution of keratin in human squamous cell carcinoma cells. The left panel shows the control experiment. White: Keratin. Courtesy: 2018 © Yanagi T. et al., Cancer Research, November 2, 2018

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