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2. Spontaneous metastasis xenograft models link CD44 isoform 4 to angiogenesis, hypoxia, EMT and mitochondria‐related pathways in colorectal cancer

Author

Everest‐Dass, Arun, primary, Nersisyan, Stepan, additional, Maar, Hanna, additional, Novosad, Victor, additional, Schröder‐Schwarz, Jennifer, additional, Freytag, Vera, additional, Stuke, Johanna L., additional, Beine, Mia C., additional, Schiecke, Alina, additional, Haider, Marie‐Therese, additional, Kriegs, Malte, additional, Elakad, Omar, additional, Bohnenberger, Hanibal, additional, Conradi, Lena‐Christin, additional, Raygorodskaya, Maria, additional, Krause, Linda, additional, von Itzstein, Mark, additional, Tonevitsky, Alexander, additional, Schumacher, Udo, additional, Maltseva, Diana, additional, Wicklein, Daniel, additional, and Lange, Tobias, additional

Published
2023
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3. Spontaneous metastasis xenograft models link CD44 isoform 4 to angiogenesis, hypoxia, EMT and mitochondria‐related pathways in colorectal cancer.

Author

Everest‐Dass, Arun, Nersisyan, Stepan, Maar, Hanna, Novosad, Victor, Schröder‐Schwarz, Jennifer, Freytag, Vera, Stuke, Johanna L., Beine, Mia C., Schiecke, Alina, Haider, Marie‐Therese, Kriegs, Malte, Elakad, Omar, Bohnenberger, Hanibal, Conradi, Lena‐Christin, Raygorodskaya, Maria, Krause, Linda, von Itzstein, Mark, Tonevitsky, Alexander, Schumacher, Udo, and Maltseva, Diana

Abstract

Hematogenous metastasis limits the survival of colorectal cancer (CRC) patients. Here, we illuminated the roles of CD44 isoforms in this process. Isoforms 3 and 4 were predominantly expressed in CRC patients. CD44 isoform 4 indicated poor outcome and correlated with epithelial–mesenchymal transition (EMT) and decreased oxidative phosphorylation (OxPhos) in patients; opposite associations were found for isoform 3. Pan‐CD44 knockdown (kd) independently impaired primary tumor formation and abrogated distant metastasis in CRC xenografts. The xenograft tumors mainly expressed the clinically relevant CD44 isoforms 3 and 4. Both isoforms were enhanced in the paranecrotic, hypoxic tumor regions but were generally absent in lung metastases. Upon CD44 kd, tumor angiogenesis was increased in the paranecrotic areas, accompanied by reduced hypoxia‐inducible factor‐1α and CEACAM5 but increased E‐cadherin expression. Mitochondrial genes and proteins were induced upon pan‐CD44 kd, as were OxPhos genes. Hypoxia increased VEGF release from tumor spheres, particularly upon CD44 kd. Genes affected upon CD44 kd in xenografts specifically overlapped concordantly with genes correlating with CD44 isoform 4 (but not isoform 3) in patients, validating the clinical relevance of the used model and highlighting the metastasis‐promoting role of CD44 isoform 4. [ABSTRACT FROM AUTHOR]

Published
2024
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4. Specificity of viscumin revised. As probed with a printed glycan array

Author

Shilova, Nadezhda, primary, Bovin, Nicolai, additional, Maltseva, Diana, additional, Polyakova, Svetlana, additional, Sablina, Marina, additional, Niwa, Hideaki, additional, Zakharova, Galina, additional, Raygorodskaya, Maria, additional, Bufeeva, Lyuba, additional, Belyi, Yury, additional, Hushpulian, Dmitry, additional, and Tonevitsky, Alexander, additional

Published
2022
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6. Low expression of CD24 is associated with poor survival in colorectal cancer

Author

Nersisyan, Stepan, primary, Ahlers, Ann-Kristin, additional, Lange, Tobias, additional, Wicklein, Daniel, additional, Galatenko, Alexei, additional, Bohnenberger, Hanibal, additional, Elakad, Omar, additional, Conradi, Lena-Christin, additional, Genduso, Sandra, additional, Maar, Hanna, additional, Schiecke, Alina, additional, Maltseva, Diana, additional, Raygorodskaya, Maria, additional, Makarova, Julia, additional, Schumacher, Udo, additional, and Tonevitsky, Alexander, additional

Published
2022
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8. Knockdown of the α5 laminin chain affects differentiation of colorectal cancer cells and their sensitivity to chemotherapy

Author

Maltseva, Diana, Raygorodskaya, Maria, Knyazev, Evgeny, Zgoda, Victor, Tikhonova, Olga, Zaidi, Shan, Nikulin, Sergey, Baranova, Ancha, Turchinovich, Andrey, Rodin, Sergey, Tonevitsky, Alexander, Maltseva, Diana, Raygorodskaya, Maria, Knyazev, Evgeny, Zgoda, Victor, Tikhonova, Olga, Zaidi, Shan, Nikulin, Sergey, Baranova, Ancha, Turchinovich, Andrey, Rodin, Sergey, and Tonevitsky, Alexander

Abstract

The interaction of tumor cells with the extracellular matrix (ECM) may affect the rate of cancer progression and metastasis. One of the major components of ECM are laminins, the heterotrimeric glycoproteins consisting of α-, β-, and γ-chains (αβγ). Laminins interact with their cell surface receptors and, thus, regulate multiple cellular processes. In this work, we demonstrate that shRNA-mediated knockdown of the α5 laminin chain results in Wnt- and mTORC1-dependent partial dedifferentiation of colorectal cancer cells. Furthermore, we showed that this dedifferentiation involved activation of ER-stress signaling, pathway promoting the sensitivity of cells to 5-fluorouracil.

Published
2020
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9. Knockdown of the α5 laminin chain affects differentiation of colorectal cancer cells and their sensitivity to chemotherapy

Author

Maltseva, Diana, primary, Raygorodskaya, Maria, additional, Knyazev, Evgeny, additional, Zgoda, Victor, additional, Tikhonova, Olga, additional, Zaidi, Shan, additional, Nikulin, Sergey, additional, Baranova, Ancha, additional, Turchinovich, Andrey, additional, Rodin, Sergey, additional, and Tonevitsky, Alexander, additional

Published
2020
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