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10. DLIC1, but not DLIC2, is upregulated in colon cancer and this contributes to proliferative overgrowth and migratory characteristics of cancer cells.

Author

Even, Ipek, Reidenbach, Sonja, Schlechter, Tanja, Berns, Nicola, Herold, Rosanna, Roth, Wilfried, Krunic, Damir, Riechmann, Veit, and Hofmann, Ilse

Subjects
COLON cancer, CANCER cell proliferation, IMMUNOHISTOCHEMISTRY, GENE expression, MICROTUBULES, CYTOPLASM
Abstract

Cytoplasmic dynein‐1 is a large minus‐end‐directed microtubule motor complex involved in membrane trafficking, organelle positioning, and microtubule organization. The roles of dynein light intermediate chains (DLICs; DLIC1 and DLIC2) within the complex are, however, still largely undefined. In this study, we investigated the possible roles of DLICs in epithelial homeostasis and colon cancer development. Mutant clonal analysis of Drosophila Dlic in the follicular epithelium of Drosophila ovary showed defects in nuclear positioning, epithelial integrity, and apical cell polarity. Consistently, knockdown of human DLIC1 and DLIC2 in colon carcinoma cells resulted in damaged epithelial organization, disturbed lumen formation, and impaired apical polarity establishment in three‐dimensional cell culture. Depletion of DLIC1 and DLIC2 led to reduced proliferation, enhanced apoptosis rates, disrupted mitotic spindle assembly, and induction of G2/M arrest in cell cycle progression. Moreover, reduced levels of DLIC1 in contrast to DLIC2 impaired the migratory ability. On the other hand, immunohistochemical examination of human colorectal tissue samples and further colorectal cancer dataset analysis showed a significant upregulation for DLIC1 in tumors, whereas DLIC2 expression was unchanged. In addition, the overexpression of DLIC1 caused increased proliferation, decreased apoptosis and enhanced migration, whereas DLIC2 overexpression did not result in any significant changes. Together, these results indicate that DLIC1 and DLIC2 contribute to the establishment and maintenance of epithelial homeostasis. Furthermore, these findings present the first evidence that DLIC1 and DLIC2 have distinct roles in colon cancer development and that DLIC1 may contribute to proliferative overgrowth and migratory characteristics. Cytoplasmic dynein 1 complexes contain either the dynein light intermediate chain (DLIC) 1 or 2 subunit, but not both of them, suggesting diverse dynein functions in respect to subunit heterogeneity. We investigated the possible roles of DLICs in epithelial homeostasis and colon cancer development. Increased levels of DLIC1, but not DLIC2, enhance proliferation, decrease apoptosis, and induce migration. Moreover, colon tumors show upregulation for DLIC1, but not for DLIC2. Diverse molecular interaction partners of DLIC1 and DLIC2 may define their discrete regulatory roles and different contributions to colon cancer development. [ABSTRACT FROM AUTHOR]

Published
2019
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13. The genome of the model beetle and pest Tribolium castaneum.

Author

Richards, Stephen, Gibbs, Richard A, Weinstock, George M, Brown, Susan J, Denell, Robin, Beeman, Richard W, Gibbs, Richard, Bucher, Gregor, Friedrich, Markus, Grimmelikhuijzen, Cornelis J P, Klingler, Martin, Lorenzen, Marce, Roth, Siegfried, Schröder, Reinhard, Tautz, Diethard, Zdobnov, Evgeny M, Muzny, Donna, Attaway, Tony, Bell, Stephanie, Buhay, Christian J, Chandrabose, Mimi N, Chavez, Dean, Clerk-Blankenburg, Kerstin P, Cree, Andrew, Dao, Marvin, Davis, Clay, Chacko, Joseph, Dinh, Huyen, Dugan-Rocha, Shannon, Fowler, Gerald, Garner, Toni T, Garnes, Jeffrey, Gnirke, Andreas, Hawes, Alica, Hernandez, Judith, Hines, Sandra, Holder, Michael, Hume, Jennifer, Jhangiani, Shalini N, Joshi, Vandita, Khan, Ziad Mohid, Jackson, LaRonda, Kovar, Christie, Kowis, Andrea, Lee, Sandra, Lewis, Lora R, Margolis, Jon, Morgan, Margaret, Nazareth, Lynne V, Nguyen, Ngoc, Okwuonu, Geoffrey, Parker, David, Ruiz, San-Juana, Santibanez, Jireh, Savard, Joël, Scherer, Steven E, Schneider, Brian, Sodergren, Erica, Vattahil, Selina, Villasana, Donna, White, Courtney S, Wright, Rita, Park, Yoonseong, Lord, Jeff, Oppert, Brenda, Brown, Susan, Wang, Liangjiang, Weinstock, George, Liu, Yue, Worley, Kim, Elsik, Christine G, Reese, Justin T, Elhaik, Eran, Landan, Giddy, Graur, Dan, Arensburger, Peter, Atkinson, Peter, Beidler, Jim, Demuth, Jeffery P, Drury, Douglas W, Du, Yu-Zhou, Fujiwara, Haruhiko, Maselli, Vincenza, Osanai, Mizuko, Robertson, Hugh M, Tu, Zhijian, Wang, Jian-jun, Wang, Suzhi, Song, Henry, Zhang, Lan, Werner, Doreen, Stanke, Mario, Morgenstern, Burkhard, Solovyev, Victor, Kosarev, Peter, Brown, Garth, Chen, Hsiu-Chuan, Ermolaeva, Olga, Hlavina, Wratko, Kapustin, Yuri, Kiryutin, Boris, Kitts, Paul, Maglott, Donna, Pruitt, Kim, Sapojnikov, Victor, Souvorov, Alexandre, Mackey, Aaron J, Waterhouse, Robert M, Wyder, Stefan, Kriventseva, Evgenia V, Kadowaki, Tatsuhiko, Bork, Peer, Aranda, Manuel, Bao, Riyue, Beermann, Anke, Berns, Nicola, Bolognesi, Renata, Bonneton, François, Bopp, Daniel, Butts, Thomas, Chaumot, Arnaud, Denell, Robin E, Ferrier, David E K, Gordon, Cassondra M, Jindra, Marek, Lan, Que, Lattorff, H Michael G, Laudet, Vincent, von Levetsow, Cornelia, Liu, Zhenyi, Lutz, Rebekka, Lynch, Jeremy A, da Fonseca, Rodrigo Nunes, Posnien, Nico, Reuter, Rolf, Schinko, Johannes B, Schmitt, Christian, Schoppmeier, Michael, Shippy, Teresa D, Simonnet, Franck, Marques-Souza, Henrique, Tomoyasu, Yoshinori, Trauner, Jochen, Van der Zee, Maurijn, Vervoort, Michel, Wittkopp, Nadine, Wimmer, Ernst A, Yang, Xiaoyun, Jones, Andrew K, Sattelle, David B, Ebert, Paul R, Nelson, David, Scott, Jeffrey G, Muthukrishnan, Subbaratnam, Kramer, Karl J, Arakane, Yasuyuki, Zhu, Qingsong, Hogenkamp, David, Dixit, Radhika, Jiang, Haobo, Zou, Zhen, Marshall, Jeremy, Elpidina, Elena, Vinokurov, Konstantin, Oppert, Cris, Evans, Jay, Lu, Zhiqiang, Zhao, Picheng, Sumathipala, Niranji, Altincicek, Boran, Vilcinskas, Andreas, Williams, Michael, Hultmark, Dan, Hetru, Charles, Hauser, Frank, Cazzamali, Giuseppe, Williamson, Michael, Li, Bin, Tanaka, Yoshiaki, Predel, Reinhard, Neupert, Susanne, Schachtner, Joachim, Verleyen, Peter, Raible, Florian, Walden, Kimberly K O, Angeli, Sergio, Forêt, Sylvain, Schuetz, Stefan, Maleszka, Ryszard, Miller, Sherry C, Grossmann, Daniela, Richards, Stephen, Gibbs, Richard A, Weinstock, George M, Brown, Susan J, Denell, Robin, Beeman, Richard W, Gibbs, Richard, Bucher, Gregor, Friedrich, Markus, Grimmelikhuijzen, Cornelis J P, Klingler, Martin, Lorenzen, Marce, Roth, Siegfried, Schröder, Reinhard, Tautz, Diethard, Zdobnov, Evgeny M, Muzny, Donna, Attaway, Tony, Bell, Stephanie, Buhay, Christian J, Chandrabose, Mimi N, Chavez, Dean, Clerk-Blankenburg, Kerstin P, Cree, Andrew, Dao, Marvin, Davis, Clay, Chacko, Joseph, Dinh, Huyen, Dugan-Rocha, Shannon, Fowler, Gerald, Garner, Toni T, Garnes, Jeffrey, Gnirke, Andreas, Hawes, Alica, Hernandez, Judith, Hines, Sandra, Holder, Michael, Hume, Jennifer, Jhangiani, Shalini N, Joshi, Vandita, Khan, Ziad Mohid, Jackson, LaRonda, Kovar, Christie, Kowis, Andrea, Lee, Sandra, Lewis, Lora R, Margolis, Jon, Morgan, Margaret, Nazareth, Lynne V, Nguyen, Ngoc, Okwuonu, Geoffrey, Parker, David, Ruiz, San-Juana, Santibanez, Jireh, Savard, Joël, Scherer, Steven E, Schneider, Brian, Sodergren, Erica, Vattahil, Selina, Villasana, Donna, White, Courtney S, Wright, Rita, Park, Yoonseong, Lord, Jeff, Oppert, Brenda, Brown, Susan, Wang, Liangjiang, Weinstock, George, Liu, Yue, Worley, Kim, Elsik, Christine G, Reese, Justin T, Elhaik, Eran, Landan, Giddy, Graur, Dan, Arensburger, Peter, Atkinson, Peter, Beidler, Jim, Demuth, Jeffery P, Drury, Douglas W, Du, Yu-Zhou, Fujiwara, Haruhiko, Maselli, Vincenza, Osanai, Mizuko, Robertson, Hugh M, Tu, Zhijian, Wang, Jian-jun, Wang, Suzhi, Song, Henry, Zhang, Lan, Werner, Doreen, Stanke, Mario, Morgenstern, Burkhard, Solovyev, Victor, Kosarev, Peter, Brown, Garth, Chen, Hsiu-Chuan, Ermolaeva, Olga, Hlavina, Wratko, Kapustin, Yuri, Kiryutin, Boris, Kitts, Paul, Maglott, Donna, Pruitt, Kim, Sapojnikov, Victor, Souvorov, Alexandre, Mackey, Aaron J, Waterhouse, Robert M, Wyder, Stefan, Kriventseva, Evgenia V, Kadowaki, Tatsuhiko, Bork, Peer, Aranda, Manuel, Bao, Riyue, Beermann, Anke, Berns, Nicola, Bolognesi, Renata, Bonneton, François, Bopp, Daniel, Butts, Thomas, Chaumot, Arnaud, Denell, Robin E, Ferrier, David E K, Gordon, Cassondra M, Jindra, Marek, Lan, Que, Lattorff, H Michael G, Laudet, Vincent, von Levetsow, Cornelia, Liu, Zhenyi, Lutz, Rebekka, Lynch, Jeremy A, da Fonseca, Rodrigo Nunes, Posnien, Nico, Reuter, Rolf, Schinko, Johannes B, Schmitt, Christian, Schoppmeier, Michael, Shippy, Teresa D, Simonnet, Franck, Marques-Souza, Henrique, Tomoyasu, Yoshinori, Trauner, Jochen, Van der Zee, Maurijn, Vervoort, Michel, Wittkopp, Nadine, Wimmer, Ernst A, Yang, Xiaoyun, Jones, Andrew K, Sattelle, David B, Ebert, Paul R, Nelson, David, Scott, Jeffrey G, Muthukrishnan, Subbaratnam, Kramer, Karl J, Arakane, Yasuyuki, Zhu, Qingsong, Hogenkamp, David, Dixit, Radhika, Jiang, Haobo, Zou, Zhen, Marshall, Jeremy, Elpidina, Elena, Vinokurov, Konstantin, Oppert, Cris, Evans, Jay, Lu, Zhiqiang, Zhao, Picheng, Sumathipala, Niranji, Altincicek, Boran, Vilcinskas, Andreas, Williams, Michael, Hultmark, Dan, Hetru, Charles, Hauser, Frank, Cazzamali, Giuseppe, Williamson, Michael, Li, Bin, Tanaka, Yoshiaki, Predel, Reinhard, Neupert, Susanne, Schachtner, Joachim, Verleyen, Peter, Raible, Florian, Walden, Kimberly K O, Angeli, Sergio, Forêt, Sylvain, Schuetz, Stefan, Maleszka, Ryszard, Miller, Sherry C, and Grossmann, Daniela

Abstract

Tribolium castaneum is a representative of earth’s most numerous eukaryotic order, a powerful model organism for the study of generalized insect development, and also an important pest of stored agricultural products. We describe its genome sequence here. This omnivorous beetle has evolved an ability to interact with a diverse chemical environment as evidenced by large expansions in odorant and gustatory receptors, as well as p450 and other detoxification enzymes. Developmental patterns in Tribolium are more representative of other arthropods than those found in Drosophila, a fact represented in gene content and function. For one, Tribolium has retained more ancestral genes involved in cell-cell communication than Drosophila, and some are expressed in the growth zone crucial for axial elongation in short germ development. Systemic RNAi in T. castaneum appears to use mechanisms distinct from those found in C. elegans, but nevertheless offers similar power for the elucidation of gene function and identification of targets for selective insect control.

Published
2008

16. A genome-scale in vivo RNAi analysis of epithelial development in Drosophila identifies new proliferation domains outside of the stem cell niche.

Author

Berns, Nicola, Woichansky, Innokenty, Friedrichsen, Steffen, Kraft, Nadine, and Riechmann*, Veit

Subjects
*EPITHELIUM, *DEVELOPMENTAL cytology, *DROSOPHILA as laboratory animals, *CELL proliferation, *STEM cell culture, *CELL division, *PHYSIOLOGY
Abstract

The Drosophila oogenesis system provides an excellent model to study the development of epithelial tissues. Here, we report the first genome-scale in vivo RNA interference (RNAi) screen for genes controlling epithelial development. By directly analysing cell and tissue architecture we identified 1125 genes, which we assigned to seven different functions in epithelial formation and homeostasis. We validated the significance of our screen by generating mutants for Vps60, a component of the endosomal sorting complexes required for transport (ESCRT) machinery. This analysis provided new insights into spatiotemporal control of cell proliferation in the follicular epithelium. Previous studies have identified signals controlling divisions in the follicle stem cell niche. However, 99% of cell divisions occur outside of the niche and it is unclear how these divisions are controlled. Our data distinguish two new domains outside of the stem cell niche where there are differing controls on proliferation. One domain abuts the niche and is characterised by ESCRT, Notch and JAK/STAT-mediated control of proliferation. Adjacent to this domain, another domain is defined by loss of the impact of ESCRT on cell division. Thus, during development epithelial cells pass through a variety of microenvironments that exert different modes of proliferation control. The switch between these modes might reflect a decrease in the 'stemness' of epithelial cells over time. [ABSTRACT FROM AUTHOR]

Published
2014
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18. The genome of the model beetle and pest Tribolium castaneum.

Author

Richards S, Gibbs RA, Weinstock GM, Brown SJ, Denell R, Beeman RW, Gibbs R, Beeman RW, Brown SJ, Bucher G, Friedrich M, Grimmelikhuijzen CJ, Klingler M, Lorenzen M, Richards S, Roth S, Schröder R, Tautz D, Zdobnov EM, Muzny D, Gibbs RA, Weinstock GM, Attaway T, Bell S, Buhay CJ, Chandrabose MN, Chavez D, Clerk-Blankenburg KP, Cree A, Dao M, Davis C, Chacko J, Dinh H, Dugan-Rocha S, Fowler G, Garner TT, Garnes J, Gnirke A, Hawes A, Hernandez J, Hines S, Holder M, Hume J, Jhangiani SN, Joshi V, Khan ZM, Jackson L, Kovar C, Kowis A, Lee S, Lewis LR, Margolis J, Morgan M, Nazareth LV, Nguyen N, Okwuonu G, Parker D, Richards S, Ruiz SJ, Santibanez J, Savard J, Scherer SE, Schneider B, Sodergren E, Tautz D, Vattahil S, Villasana D, White CS, Wright R, Park Y, Beeman RW, Lord J, Oppert B, Lorenzen M, Brown S, Wang L, Savard J, Tautz D, Richards S, Weinstock G, Gibbs RA, Liu Y, Worley K, Weinstock G, Elsik CG, Reese JT, Elhaik E, Landan G, Graur D, Arensburger P, Atkinson P, Beeman RW, Beidler J, Brown SJ, Demuth JP, Drury DW, Du YZ, Fujiwara H, Lorenzen M, Maselli V, Osanai M, Park Y, Robertson HM, Tu Z, Wang JJ, Wang S, Richards S, Song H, Zhang L, Sodergren E, Werner D, Stanke M, Morgenstern B, Solovyev V, Kosarev P, Brown G, Chen HC, Ermolaeva O, Hlavina W, Kapustin Y, Kiryutin B, Kitts P, Maglott D, Pruitt K, Sapojnikov V, Souvorov A, Mackey AJ, Waterhouse RM, Wyder S, Zdobnov EM, Zdobnov EM, Wyder S, Kriventseva EV, Kadowaki T, Bork P, Aranda M, Bao R, Beermann A, Berns N, Bolognesi R, Bonneton F, Bopp D, Brown SJ, Bucher G, Butts T, Chaumot A, Denell RE, Ferrier DE, Friedrich M, Gordon CM, Jindra M, Klingler M, Lan Q, Lattorff HM, Laudet V, von Levetsow C, Liu Z, Lutz R, Lynch JA, da Fonseca RN, Posnien N, Reuter R, Roth S, Savard J, Schinko JB, Schmitt C, Schoppmeier M, Schröder R, Shippy TD, Simonnet F, Marques-Souza H, Tautz D, Tomoyasu Y, Trauner J, Van der Zee M, Vervoort M, Wittkopp N, Wimmer EA, Yang X, Jones AK, Sattelle DB, Ebert PR, Nelson D, Scott JG, Beeman RW, Muthukrishnan S, Kramer KJ, Arakane Y, Beeman RW, Zhu Q, Hogenkamp D, Dixit R, Oppert B, Jiang H, Zou Z, Marshall J, Elpidina E, Vinokurov K, Oppert C, Zou Z, Evans J, Lu Z, Zhao P, Sumathipala N, Altincicek B, Vilcinskas A, Williams M, Hultmark D, Hetru C, Jiang H, Grimmelikhuijzen CJ, Hauser F, Cazzamali G, Williamson M, Park Y, Li B, Tanaka Y, Predel R, Neupert S, Schachtner J, Verleyen P, Raible F, Bork P, Friedrich M, Walden KK, Robertson HM, Angeli S, Forêt S, Bucher G, Schuetz S, Maleszka R, Wimmer EA, Beeman RW, Lorenzen M, Tomoyasu Y, Miller SC, Grossmann D, and Bucher G

Subjects
Animals, Base Composition, Body Patterning genetics, Cytochrome P-450 Enzyme System genetics, DNA Transposable Elements genetics, Growth and Development genetics, Humans, Insecticides pharmacology, Neurotransmitter Agents genetics, Oogenesis genetics, Phylogeny, Proteome genetics, RNA Interference, Receptors, G-Protein-Coupled genetics, Receptors, Odorant genetics, Repetitive Sequences, Nucleic Acid genetics, Taste genetics, Telomere genetics, Tribolium classification, Tribolium embryology, Tribolium physiology, Vision, Ocular genetics, Genes, Insect genetics, Genome, Insect genetics, Tribolium genetics
Abstract

Tribolium castaneum is a member of the most species-rich eukaryotic order, a powerful model organism for the study of generalized insect development, and an important pest of stored agricultural products. We describe its genome sequence here. This omnivorous beetle has evolved the ability to interact with a diverse chemical environment, as shown by large expansions in odorant and gustatory receptors, as well as P450 and other detoxification enzymes. Development in Tribolium is more representative of other insects than is Drosophila, a fact reflected in gene content and function. For example, Tribolium has retained more ancestral genes involved in cell-cell communication than Drosophila, some being expressed in the growth zone crucial for axial elongation in short-germ development. Systemic RNA interference in T. castaneum functions differently from that in Caenorhabditis elegans, but nevertheless offers similar power for the elucidation of gene function and identification of targets for selective insect control.

Published
2008
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