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Cell Growth and Development

Caveolin-Induced Activation of the Phosphatidylinositol 3-Kinase/Akt Pathway Increases Arsenite Cytotoxicity

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Pages 2407-2414 | Received 09 Aug 2002, Accepted 07 Jan 2003, Published online: 27 Mar 2023

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Maria Shatz & Mordechai Liscovitch. (2008) Caveolin-1: A tumor-promoting role in human cancer. International Journal of Radiation Biology 84:3, pages 177-189.
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Likun Li, Cheng Hui Ren, Salahaldin A. Tahir, Chengzhen Ren & Timothy C. Thompson. (2003) Caveolin-1 Maintains Activated Akt in Prostate CancerCells through Scaffolding Domain Binding Site Interactions with andInhibition of Serine/Threonine Protein Phosphatases PP1 andPP2A. Molecular and Cellular Biology 23:24, pages 9389-9404.
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Q Liu, J Qiu, M Liang, J Golinski, K van Leyen, J E Jung, Z You, E H Lo, A Degterev & M J Whalen. (2014) Akt and mTOR mediate programmed necrosis in neurons. Cell Death & Disease 5:2, pages e1084-e1084.
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Yaoyao Zhan, Liang Wang, Jing Liu, Keli Ma, Cuiping Liu, Yuan Zhang & Wei Zou. (2013) Choline Plasmalogens Isolated from Swine Liver Inhibit Hepatoma Cell Proliferation Associated with Caveolin-1/Akt Signaling. PLoS ONE 8:10, pages e77387.
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Hironori Motoshige, Kyohei Oyama, Kiyoshi Takahashi & Koichi Sakurai. (2012) Involvement of Phosphatidylinositol 3-Kinase/Akt Pathway in Gemcitabine-Induced Apoptosis-Like Cell Death in Insulinoma Cell Line INS-1. Biological and Pharmaceutical Bulletin 35:11, pages 1932-1940.
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Yang Jin, Seon-Jin Lee, Richard D. Minshall & Augustine M. K. Choi. (2011) Caveolin-1: a critical regulator of lung injury. American Journal of Physiology-Lung Cellular and Molecular Physiology 300:2, pages L151-L160.
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Jae Hong Park & Ho Jae Han. (2009) Caveolin-1 plays important role in EGF-induced migration and proliferation of mouse embryonic stem cells: involvement of PI3K/Akt and ERK. American Journal of Physiology-Cell Physiology 297:4, pages C935-C944.
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Pithi Chanvorachote, Ubonthip Nimmannit, Yongju Lu, Siera Talbott, Bing-Hua Jiang & Yon Rojanasakul. (2009) Nitric Oxide Regulates Lung Carcinoma Cell Anoikis through Inhibition of Ubiquitin-Proteasomal Degradation of Caveolin-1. Journal of Biological Chemistry 284:41, pages 28476-28484.
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Marek Los, Soumya Panigrahi, Iran Rashedi, Sanat Mandal, Joerg Stetefeld, Frank Essmann & Klaus Schulze-Osthoff. (2009) Apoptin, a tumor-selective killer. Biochimica et Biophysica Acta (BBA) - Molecular Cell Research 1793:8, pages 1335-1342.
Crossref
Marek Los, Iran Rashedi, Soumya Panigrahi, Thomas Klonisch & Klaus Schulze-Osthoff. 2009. The Impact of Tumor Biology on Cancer Treatment and Multidisciplinary Strategies. The Impact of Tumor Biology on Cancer Treatment and Multidisciplinary Strategies 19 37 .
Jacky G. Goetz, Patrick Lajoie, Sam M. Wiseman & Ivan R. Nabi. (2008) Caveolin-1 in tumor progression: the good, the bad and the ugly. Cancer and Metastasis Reviews 27:4, pages 715-735.
Crossref
Min-Jung Kim, Soon-Young Choi, In-Chul Park, Sang-Gu Hwang, Changil Kim, Young-Hyun Choi, Haekwon Kim, Kee-Ho Lee & Su-Jae Lee. (2008) Opposing Roles of c-Jun NH2-Terminal Kinase and p38 Mitogen-Activated Protein Kinase in the Cellular Response to Ionizing Radiation in Human Cervical Cancer Cells. Molecular Cancer Research 6:11, pages 1718-1731.
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Laura C. Matthews, Michael J. Taggart & Melissa Westwood. (2008) Modulation of Caveolin-1 Expression Can Affect Signalling through the Phosphatidylinositol 3-Kinase/Akt Pathway and Cellular Proliferation in Response to Insulin-Like Growth Factor I. Endocrinology 149:10, pages 5199-5208.
Crossref
Andrew F. G. Quest, Jorge L. Gutierrez-Pajares & Vicente A. Torres. (2008) Caveolin-1: an ambiguous partner in cell signalling and cancer. Journal of Cellular and Molecular Medicine 12:4, pages 1130-1150.
Crossref
S E Elsheikh, A R Green, E A Rakha, R M Samaka, A A Ammar, D Powe, J S Reis-Filho & I O Ellis. (2008) Caveolin 1 and Caveolin 2 are associated with breast cancer basal-like and triple-negative immunophenotype. British Journal of Cancer 99:2, pages 327-334.
Crossref
Kwiyeom Yoon, Eun Joo Jung & Soo Young Lee. (2008) TRAF6-mediated regulation of the PI3 kinase (PI3K)–Akt–GSK3β cascade is required for TNF-induced cell survival. Biochemical and Biophysical Research Communications 371:1, pages 118-121.
Crossref
Aline Chrétien, Neil Piront, Edouard Delaive, Catherine Demazy, Noëlle Ninane & Olivier Toussaint. (2008) Increased abundance of cytoplasmic and nuclear caveolin 1 in human diploid fibroblasts in H 2 O 2 -induced premature senescence and interplay with p38α MAPK . FEBS Letters 582:12, pages 1685-1692.
Crossref
Subbareddy Maddika, Sudharsana Rao Ande, Emilia Wiechec, Lise Lotte Hansen, Sebastian Wesselborg & Marek Los. (2008) Akt-mediated phosphorylation of CDK2 regulates its dual role in cell cycle progression and apoptosis. Journal of Cell Science 121:7, pages 979-988.
Crossref
Brian P. Head, Hemal H. Patel, Yasuo M. Tsutsumi, Yue Hu, Trisha Mejia, Rosalia C. Mora, Paul A. Insel, David M. Roth, John C. Drummond & Piyush M. Patel. (2007) Caveolin‐1 expression is essential for N ‐methyl‐ D ‐aspartate receptor‐mediated Src and extracellular signal‐regulated kinase 1/2 activation and protection of primary neurons from ischemic cell death . The FASEB Journal 22:3, pages 828-840.
Crossref
Rebecca S. Henkhaus, Upal Kunal Basu Roy, Dora Cavallo-Medved, Bonnie F. Sloane, Eugene W. Gerner & Natalia A. Ignatenko. (2008) Caveolin-1-Mediated Expression and Secretion of Kallikrein 6 in Colon Cancer Cells. Neoplasia 10:2, pages 140-148.
Crossref
Hemal H. PatelFiona Murray & Paul A. Insel. (2008) Caveolae as Organizers of Pharmacologically Relevant Signal Transduction Molecules. Annual Review of Pharmacology and Toxicology 48:1, pages 359-391.
Crossref
E. Sarró, O. Tornavaca, M. Plana, A. Meseguer & E. Itarte. (2008) Phosphoinositide 3-kinase inhibitors protect mouse kidney cells from cyclosporine-induced cell death. Kidney International 73:1, pages 77-85.
Crossref
Chao-Chi Ho, Sung-Hsin Kuo, Pei-Hsin Huang, Hsin-Yi Huang, Chih-Hsin Yang & Pan-Chyr Yang. (2008) Caveolin-1 expression is significantly associated with drug resistance and poor prognosis in advanced non-small cell lung cancer patients treated with gemcitabine-based chemotherapy. Lung Cancer 59:1, pages 105-110.
Crossref
H. H. Patel, F. Murray & P. A. Insel. 2008. Protein-Protein Interactions as New Drug Targets. Protein-Protein Interactions as New Drug Targets 167 184 .
Ping Wu, Baoju Qi, Hua Zhu, Yamin Zheng, Fei Li & Jianwen Chen. (2007) Suppression of staurosporine-mediated apoptosis in Hs578T breast cells through inhibition of neutral-sphingomyelinase by caveolin-1. Cancer Letters 256:1, pages 64-72.
Crossref
Gayle M. Smythe & Thomas A. Rando. (2006) Altered caveolin-3 expression disrupts PI(3) kinase signaling leading to death of cultured muscle cells. Experimental Cell Research 312:15, pages 2816-2825.
Crossref
Vicente A. Torres, Julio C. Tapia, Diego A. Rodríguez, Mario Párraga, Pamela Lisboa, Margarita Montoya, Lisette Leyton & Andrew F. G. Quest. (2006) Caveolin-1 controls cell proliferation and cell death by suppressing expression of the inhibitor of apoptosis protein survivin. Journal of Cell Science 119:9, pages 1812-1823.
Crossref
Sudhakar Chintharlapalli, Sabitha Papineni & Stephen Safe. (2006) 1,1-Bis(3′-indolyl)-1-( p -substituted phenyl)methanes inhibit colon cancer cell and tumor growth through PPARγ-dependent and PPARγ-independent pathways . Molecular Cancer Therapeutics 5:5, pages 1362-1370.
Crossref
Wassim Kassouf, Sudhakar Chintharlapalli, Maen Abdelrahim, Gina Nelkin, Stephen Safe & Ashish M. Kamat. (2006) Inhibition of Bladder Tumor Growth by 1,1-Bis(3′-Indolyl)-1-( p -Substitutedphenyl)Methanes: A New Class of Peroxisome Proliferator-Activated Receptor γ Agonists . Cancer Research 66:1, pages 412-418.
Crossref
Sudhakar Chintharlapalli, Sabitha Papineni, Seung Joon Baek, Shengxi Liu & Stephen Safe. (2005) 1,1-Bis(3′-indolyl)-1-( p -substitutedphenyl)methanes Are Peroxisome Proliferator-Activated Receptor γ Agonists but Decrease HCT-116 Colon Cancer Cell Survival through Receptor-Independent Activation of Early Growth Response-1 and Nonsteroidal Anti-Inflammatory Drug-Activated Gene-1 . Molecular Pharmacology 68:6, pages 1782-1792.
Crossref
Seung Bum Lee, Sung Hee Hong, Hoguen Kim & Hong-Duck Um. (2005) Co-induction of cell death and survival pathways by phosphoinositide 3-kinase. Life Sciences 78:1, pages 91-98.
Crossref
Maryse Remacle-Bonnet, Françoise Garrouste, Gilbert Baillat, Frédéric Andre, Jacques Marvaldi & Gilbert Pommier. (2005) Membrane Rafts Segregate Pro- from Anti-Apoptotic Insulin-Like Growth Factor-I Receptor Signaling in Colon Carcinoma Cells Stimulated by Members of the Tumor Necrosis Factor Superfamily. The American Journal of Pathology 167:3, pages 761-773.
Crossref
Sudhakar Chintharlapalli, Sabitha Papineni, Marina Konopleva, Michael Andreef, Ismael Samudio & Stephen Safe. (2005) 2-Cyano-3,12-dioxoolean-1,9-dien-28-oic Acid and Related Compounds Inhibit Growth of Colon Cancer Cells through Peroxisome Proliferator-Activated Receptor γ-Dependent and -Independent Pathways. Molecular Pharmacology 68:1, pages 119-128.
Crossref
Seung Bum Lee, Eun Sook Cho, Hyun Sook Yang, Hoguen Kim & Hong-Duck Um. (2005) Serum withdrawal kills U937 cells by inducing a positive mutual interaction between reactive oxygen species and phosphoinositide 3-kinase. Cellular Signalling 17:2, pages 197-204.
Crossref
Mingyu Xia, Minwei Wang, Shin-ichi Tashiro, Satoshi Onodera, Mutsuhiko Minami & Takashi Ikejima. (2005) Dracorhodin Perchlorate Induces A375-S2 Cell Apoptosis via Accumulation of p53 and Activation of Caspases. Biological and Pharmaceutical Bulletin 28:2, pages 226-232.
Crossref
Junsuke Igarashi. 2005. Caveolae and Lipid Rafts: Roles in Signal Transduction and the Pathogenesis of Human Disease. Caveolae and Lipid Rafts: Roles in Signal Transduction and the Pathogenesis of Human Disease 125 140 .
Eva Gonzalez, Aaron Nagiel, Alison J. Lin, David E. Golan & Thomas Michel. (2004) Small Interfering RNA-mediated Down-regulation of Caveolin-1 Differentially Modulates Signaling Pathways in Endothelial Cells. Journal of Biological Chemistry 279:39, pages 40659-40669.
Crossref
Koh Ono, Yoshitaka Iwanaga, Madoka Hirayama, Teruhisa Kawamura, Naoya Sowa & Koji Hasegawa. (2004) Contribution of caveolin-1α and Akt to TNF-α-induced cell death. American Journal of Physiology-Lung Cellular and Molecular Physiology 287:1, pages L201-L209.
Crossref
Neelanjana Ray & L. W. Enquist. (2004) Transcriptional Response of a Common Permissive Cell Type to Infection by Two Diverse Alphaherpesviruses. Journal of Virology 78:7, pages 3489-3501.
Crossref
Hao Pang, Phuong U. Le & Ivan R. Nabi. (2004) Ganglioside GM1 levels are a determinant of the extent of caveolae/raft-dependent endocytosis of cholera toxin to the Golgi apparatus. Journal of Cell Science 117:8, pages 1421-1430.
Crossref
Liat Drucker, Faina Afensiev, Judith Radnay, Hava Shapira & Michael Lishner. (2004) Co-administration of simvastatin and cytotoxic drugs is advantageous in myeloma cell lines. Anti-Cancer Drugs 15:1, pages 79-84.
Crossref
Hyang-Mi Lee, Hyung-Sung Jin, Jae-Won Park, Sun-Mi Park, Hye-Kyung Jeon & Tae H. Lee. (2003) IL-4 augments anisomycin-induced p38 activation via Akt pathway in a follicular dendritic cell (FDC)-like line. FEBS Letters 549:1-3, pages 110-114.
Crossref

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