Talks
MUC13 enhances anchorage independent survival and cooperates with YAP1 towards colorectal cancer metastasis
Presentation Type
Oral Presentation
Discipline Track
Clinical Science
Abstract Type
Research/Clinical
Abstract
About 90% of all cancer related deaths are due to the development of metastatic sites in the body. With 40-50% of all Colorectal cancer patients developing metastasis at some point during the disease, understanding the underlying mechanisms is vital. Death due to attachment from the Extracellular matrix is a natural defense against metastasis is called Anoikis. Understanding the mechanism overcoming Anoikis is an important step towards developing new therapeutic options to prevent the metastatic spread of cancer cells. We identified mucin MUC13 in correspondence with YAP1 and β-catenin as key upregulated proteins in anchorage independent survival and metastasis progression. MUC13 expression correlated with an increase in survival among SW480 cells and decrease in survival in SW620 cells when expression is loss. We found that MUC13 expression led to an increase in the formation of YAP1/β-catenin survival complex within the nucleus at 36hrs. Further we found enhanced interaction between MUC13/YAP1 and MUC13/β-catenin in the nucleus was also observed. In human CRC tissues, MUC13 and YAP1 expression was high in tumor compared to normal adjacent tumor along decrease survival among high MUC13 and YAP1 expressing tissues. When MUC13 was found in the nucleus we found a positive correlation with the total YAP1 expression. This supports the notion that MUC13 is a key factor in enhancing anchorage independence survival and CRC tumorigenesis through cooperation with YAP1 and β-catenin. This study for the first time demonstrates complex formation between MUC13, YAP1 and β-catenin, and define their role in CRC progression and metastasis.
In an isogeneic CRC cell line model, overexpression of MUC13 in non-metastatic SW480 cells (originally expressing minimal MUC13) increased anchorage independent survival and enhanced tumorigenesis compared to SW480+Vector cells. Metastatic SW620 CRC cells (highly expressing MUC13) showed a decreased anchorage independent survival and tumorigenesis after knockdown using specific shRNA targeted against MUC13, compared to its vector.
Recommended Citation
Doxtater, Kyle; Mehta, Radhika; Mishra, Utkarsh K.; Jaggi, Meena; Tripathi, Manish; and Chauhan, Subhash C., "MUC13 enhances anchorage independent survival and cooperates with YAP1 towards colorectal cancer metastasis" (2023). Research Symposium. 58.
https://scholarworks.utrgv.edu/somrs/theme1/track1/58
MUC13 enhances anchorage independent survival and cooperates with YAP1 towards colorectal cancer metastasis
About 90% of all cancer related deaths are due to the development of metastatic sites in the body. With 40-50% of all Colorectal cancer patients developing metastasis at some point during the disease, understanding the underlying mechanisms is vital. Death due to attachment from the Extracellular matrix is a natural defense against metastasis is called Anoikis. Understanding the mechanism overcoming Anoikis is an important step towards developing new therapeutic options to prevent the metastatic spread of cancer cells. We identified mucin MUC13 in correspondence with YAP1 and β-catenin as key upregulated proteins in anchorage independent survival and metastasis progression. MUC13 expression correlated with an increase in survival among SW480 cells and decrease in survival in SW620 cells when expression is loss. We found that MUC13 expression led to an increase in the formation of YAP1/β-catenin survival complex within the nucleus at 36hrs. Further we found enhanced interaction between MUC13/YAP1 and MUC13/β-catenin in the nucleus was also observed. In human CRC tissues, MUC13 and YAP1 expression was high in tumor compared to normal adjacent tumor along decrease survival among high MUC13 and YAP1 expressing tissues. When MUC13 was found in the nucleus we found a positive correlation with the total YAP1 expression. This supports the notion that MUC13 is a key factor in enhancing anchorage independence survival and CRC tumorigenesis through cooperation with YAP1 and β-catenin. This study for the first time demonstrates complex formation between MUC13, YAP1 and β-catenin, and define their role in CRC progression and metastasis.
In an isogeneic CRC cell line model, overexpression of MUC13 in non-metastatic SW480 cells (originally expressing minimal MUC13) increased anchorage independent survival and enhanced tumorigenesis compared to SW480+Vector cells. Metastatic SW620 CRC cells (highly expressing MUC13) showed a decreased anchorage independent survival and tumorigenesis after knockdown using specific shRNA targeted against MUC13, compared to its vector.