S100A11 is involved in the progression of colorectal cancer through the desmosome-catenin-TCF signaling pathway

Our plain-English summary of S100A11 is involved in the progression of colorectal cancer through the desmosome-catenin-TCF signaling pathway, by J. Zhou, H. Murata, N. Tomonobu, et al (In Vitro Cellular & Developmental Biology. Animal, 2024).

The study

• Authors: J. Zhou, H. Murata, N. Tomonobu, N. Mizuta, A. Yamakawa, K.I. Yamamoto, R. Kinoshita, M. Sakaguchi
• Journal: In Vitro Cellular & Developmental Biology. Animal
• Published: 2024;60(10):1138-1149
• Cited by: 3 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Compiling evidence has indicated that S100A11 expression at high levels is closely associated with various cancer species. Consistent with the results reported elsewhere, we have also revealed that S100A11 is highly expressed in squamous cell carcinoma, mesothelioma, and pancreatic cancers and plays a crucial role in cancer progression when secreted into extracellular fluid. Those studies are all focused on the extracellular role of S100A11. However, most of S100A11 is still present within cancer cells, although the intracellular role of S100A11 in cancer cells has not been fully elucidated. Thus, we aimed to investigate S100A11 functions within cancer cells, primarily focusing on colorectal cancer cells, whose S100A11 is abundantly present in cells and still poorly studied cancer for the protein. Our efforts revealed that overexpression of S100A11 promotes proliferation and migration, and downregulation inversely dampens those cancer behaviors. To clarify how intracellular S100A11 aids cancer cell activation, we tried to identify S100A11 binding proteins, resulting in novel binding partners in the inner membrane, many of which are desmosome proteins. Our molecular approach defined that S100A11 regulates the expression level of DSG1, a component protein of desmosome, by which S100A11 activates the TCF pathway via promoting nuclear translocation of γ-catenin from the desmosome. The identified new pathway greatly helps to comprehend S100A11's nature in colorectal cancers and others.

© 2024. The Author(s).

In plain English

This was a laboratory study of human cancer cells grown in culture, plus a commercial colon cancer tissue array. It did not study asbestos or fiber exposure, and it did not follow patients; its only human tissue samples came from that array. The authors examined a protein called S100A11 in colorectal cancer cells. Among the cancer cell lines screened, S100A11 was high in a pancreatic cancer line (PK-8) and a colorectal cancer line (HCT 116). A further test found it high in two other colorectal lines, DLD-1 and HT-29. In the tissue array, S100A11 levels tended to be higher in colorectal cancer tissue than in normal tissue. In DLD-1 cells, raising S100A11 significantly increased cell growth and movement, and lowering it reduced both. S100A11 bound several desmosome proteins (desmosomes are structures that hold cells together), including DSG1 and gamma-catenin. More S100A11 lowered DSG1, moved more gamma-catenin into the cell nucleus, and raised activity of a growth-signaling pathway called TCF. The authors concluded that S100A11 activates the TCF pathway by promoting the movement of gamma-catenin from the desmosome into the nucleus. They noted that how S100A11 controls DSG1 has not yet been worked out.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: laboratory (in vitro) study using human cancer cell lines and a human colon carcinoma tissue array
• Who was studied: Human cancer cell lines, mainly the colorectal adenocarcinoma line DLD-1, and a commercial human colon carcinoma tissue array (number of tissue samples not stated in the text)
• Exposure: No asbestos or fiber exposure was studied. The experimental factor was raising (overexpression) or lowering (siRNA knockdown) the level of the protein S100A11 in DLD-1 colorectal cancer cells.
• Main results:
  • Among the cancer cell lines screened, S100A11 expression was high in the pancreatic cancer line PK-8 and the colorectal cancer line HCT 116.
  • S100A11 was also highly expressed in the colorectal cancer lines DLD-1 and HT-29.
  • In the tissue array, S100A11 levels tended to be higher in colorectal cancer tissues than in normal tissues.
  • In DLD-1 cells, overexpression of S100A11 significantly increased cell proliferation and migration. The authors reported that silencing it suppressed both.
  • Proteins found bound to S100A11 included several desmosome proteins.
  • Overexpression of S100A11 decreased DSG1 protein levels, and downregulation of S100A11 increased them.
  • Overexpression of S100A11 increased the amount of gamma-catenin moving into the nucleus.
  • Overexpression of S100A11 increased TCF reporter activity, and knockdown of S100A11 decreased it. Overexpression also increased the proteins cyclin D1, c-Myc and TCF1/TCF7.
  • Proliferation and migration of DLD-1 cells were increased by overexpression of beta-catenin and gamma-catenin, but decreased when S100A11 was suppressed.
• The authors' conclusion: The authors concluded that S100A11 regulates the desmosome protein DSG1 and activates the TCF pathway by promoting nuclear translocation of gamma-catenin from the desmosome.
• Limitations the authors state:
  • The authors stated that how S100A11 regulates DSG1 protein levels remains to be clarified.
  • The authors stated that how much this TCF pathway contributes to proliferation and migration, compared with other S100A11 pathways, still needs to be dissected.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Colon cancer.

Medical terms in this study, explained in our Lexicon: Colorectal Cancer, Squamous Cell Carcinoma, Mesothelioma, Translocation.

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