The LIM Protein Ajuba Augments Tumor Metastasis in Colon Cancer

Colorectal cancer, along with its high potential for recurrence and metastasis, is a major health burden. Uncovering proteins and pathways required for tumor cell growth is necessary for the development of novel targeted therapies. Ajuba is a member of the LIM domain family of proteins whose expression is positively associated with numerous cancers. Our data shows that Ajuba is highly expressed in human colon cancer tissue and cell lines. Publicly available data from The Cancer Genome Atlas shows a negative correlation between survival and Ajuba expression in patients with colon cancer. To investigate its function, we transduced SW480 human colon cancer cells, with lentiviral constructs to knockdown or overexpress Ajuba protein. The transcriptome of the modified cell lines was analyzed by RNA sequencing. Among the pathways enriched in the differentially expressed genes, were cell proliferation, migration and differentiation. We confirmed our sequencing data with biological assays; cells depleted of Ajuba were less proliferative, more sensitive to irradiation, migrated less and were less efficient in colony formation. In addition, loss of Ajuba expression decreased the tumor burden in a murine model of colorectal metastasis to the liver. Taken together, our data supports that Ajuba promotes colon cancer growth, migration and metastasis and therefore is a potential candidate for targeted therapy.

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FXR silencing in human colon cancer by DNA methylation and KRAS signaling

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.00234.2013 ◽

2014 ◽

Vol 306 (1) ◽

pp. G48-G58 ◽

Cited By ~ 34

Author(s):

Ann M. Bailey ◽

Le Zhan ◽

Dipen Maru ◽

Imad Shureiqi ◽

Curtis R. Pickering ◽

...

Keyword(s):

Dna Methylation ◽

Colon Cancer ◽

Epithelial To Mesenchymal Transition ◽

Human Colon ◽

Cancer Genome ◽

The Cancer Genome Atlas ◽

Human Colon Cancer ◽

Mesenchymal Transition ◽

Cancer Genome Atlas ◽

Genome Atlas

Farnesoid X receptor (FXR) is a bile acid nuclear receptor described through mouse knockout studies as a tumor suppressor for the development of colon adenocarcinomas. This study investigates the regulation of FXR in the development of human colon cancer. We used immunohistochemistry of FXR in normal tissue ( n = 238), polyps ( n = 32), and adenocarcinomas, staged I–IV ( n = 43, 39, 68, and 9), of the colon; RT-quantitative PCR, reverse-phase protein array, and Western blot analysis in 15 colon cancer cell lines; NR1H4 promoter methylation and mRNA expression in colon cancer samples from The Cancer Genome Atlas; DNA methyltransferase inhibition; methyl-DNA immunoprecipitation (MeDIP); bisulfite sequencing; and V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) knockdown assessment to investigate FXR regulation in colon cancer development. Immunohistochemistry and quantitative RT-PCR revealed that expression and function of FXR was reduced in precancerous lesions and silenced in a majority of stage I-IV tumors. FXR expression negatively correlated with phosphatidylinositol-4, 5-bisphosphate 3 kinase signaling and the epithelial-to-mesenchymal transition. The NR1H4 promoter is methylated in ∼12% colon cancer The Cancer Genome Atlas samples, and methylation patterns segregate with tumor subtypes. Inhibition of DNA methylation and KRAS silencing both increased FXR expression. FXR expression is decreased early in human colon cancer progression, and both DNA methylation and KRAS signaling may be contributing factors to FXR silencing. FXR potentially suppresses epithelial-to-mesenchymal transition and other oncogenic signaling cascades, and restoration of FXR activity, by blocking silencing mechanisms or increasing residual FXR activity, represents promising therapeutic options for the treatment of colon cancer.

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Evaluation of metabolomics behavior of human colon cancer HT29 cell lines treated with ionic liquid graviola fruit pulp extract

Journal of Ethnopharmacology ◽

10.1016/j.jep.2021.113813 ◽

2021 ◽

Vol 270 ◽

pp. 113813

Author(s):

Djabir Daddiouaissa ◽

Azura Amid ◽

Muhamad Shirwan Abdullah Sani ◽

Ahmed A.M. Elnour

Keyword(s):

Colon Cancer ◽

Ionic Liquid ◽

Cell Lines ◽

Human Colon ◽

Ht29 Cell ◽

Fruit Pulp ◽

Human Colon Cancer

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In vitro antiproliferative activity against human colon cancer cell lines of representative 4-thiazolidinones. Part I

Bioorganic & Medicinal Chemistry Letters ◽

10.1016/j.bmcl.2005.05.093 ◽

2005 ◽

Vol 15 (17) ◽

pp. 3930-3933 ◽

Cited By ~ 92

Author(s):

Rosaria Ottanà ◽

Stefania Carotti ◽

Rosanna Maccari ◽

Ida Landini ◽

Giuseppa Chiricosta ◽

...

Keyword(s):

Colon Cancer ◽

Cell Lines ◽

Cancer Cell ◽

Antiproliferative Activity ◽

Human Colon ◽

Colon Cancer Cell ◽

Human Colon Cancer Cell ◽

Human Colon Cancer ◽

Colon Cancer Cell Lines

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Bile salt-induced apoptosis in human colon cancer cell lines involves the mitochondrial transmembrane potential but not the CD95 (Fas/Apo-1) receptor

International Journal of Colorectal Disease ◽

10.1007/s00384-004-0616-2 ◽

2004 ◽

Vol 20 (2) ◽

pp. 103-113 ◽

Cited By ~ 22

Author(s):

Frank-Peter Wachs ◽

Ren� C. Krieg ◽

Cecilia M. P. Rodrigues ◽

Helmut Messmann ◽

Frank Kullmann ◽

...

Keyword(s):

Colon Cancer ◽

Bile Salt ◽

Cell Lines ◽

Transmembrane Potential ◽

Human Colon ◽

Colon Cancer Cell ◽

Human Colon Cancer Cell ◽

Human Colon Cancer ◽

Colon Cancer Cell Lines ◽

Induced Apoptosis

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Characterization of Gastrin-Releasing Peptide and Its Receptor Aberrantly Expressed by Human Colon Cancer Cell Lines

Molecular Pharmacology ◽

10.1124/mol.58.3.601 ◽

2000 ◽

Vol 58 (3) ◽

pp. 601-607 ◽

Cited By ~ 27

Author(s):

Robert E. Carroll ◽

Denis Ostrovskiy ◽

Sean Lee ◽

Alexey Danilkovich ◽

Richard V. Benya

Keyword(s):

Colon Cancer ◽

Cell Lines ◽

Cancer Cell ◽

Human Colon ◽

Colon Cancer Cell ◽

Human Colon Cancer Cell ◽

Human Colon Cancer ◽

Gastrin Releasing Peptide ◽

Colon Cancer Cell Lines

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113 Inhibition of IDO1 Reduces Human Colon Cancer Cell Proliferation in Cell Culture and Reduces Tumor Burden in Colitis Associated Cancer Model

Gastroenterology ◽

10.1016/s0016-5085(12)60108-5 ◽

2012 ◽

Vol 142 (5) ◽

pp. S-27

Author(s):

Ameet I. Thaker ◽

Lynne R. Foster ◽

Suprada Rao ◽

William F. Stenson ◽

Matthew A. Ciorba

Keyword(s):

Cell Culture ◽

Colon Cancer ◽

Cell Proliferation ◽

Human Colon ◽

Tumor Burden ◽

Colon Cancer Cell ◽

Cancer Cell Proliferation ◽

Human Colon Cancer Cell ◽

Cancer Model ◽

Human Colon Cancer

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Expression of G-protein alpha subunits in normal rat colonocytes, azoxymethane (AOM)-induced colon tumors, and human colon cancer-derived cell lines

Gastroenterology ◽

10.1016/0016-5085(95)28119-3 ◽

1995 ◽

Vol 108 (4) ◽

pp. A954 ◽

Cited By ~ 1

Author(s):

M.J.G. Bolt ◽

R.J. Mailloux ◽

R. Wali ◽

B. Frawley ◽

B. Scaglione-Sewell ◽

...

Keyword(s):

Colon Cancer ◽

G Protein ◽

Cell Lines ◽

Human Colon ◽

Human Colon Cancer ◽

Colon Tumors ◽

Alpha Subunits ◽

Normal Rat

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Enhanced nitric oxide signaling amplifies vasorelaxation of human colon cancer feed arteries

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00368.2018 ◽

2019 ◽

Vol 316 (1) ◽

pp. H245-H254 ◽

Cited By ~ 3

Author(s):

Ninna C. S. Voss ◽

Henrik Kold-Petersen ◽

Ebbe Boedtkjer

Keyword(s):

Nitric Oxide ◽

Colon Cancer ◽

Human Colon ◽

No Synthase ◽

Cancer Tissue ◽

Solid Cancer ◽

Tumor Perfusion ◽

Normal Colon ◽

Human Colon Cancer ◽

Feed Arteries

Inadequate perfusion of solid cancer tissue results in low local nutrient and oxygen levels and accumulation of acidic waste products. Previous investigations have focused primarily on tumor blood vessel architecture, and we lack information concerning functional differences between arteries that deliver blood to solid cancer tissue versus normal tissue. Here, we use isometric myography to study resistance-sized arteries from human primary colon adenocarcinomas and matched normal colon tissue. Vasocontraction of colon cancer feed arteries in response to endothelin-1 and thromboxane stimulation is attenuated compared with normal colon arteries despite similar wall dimensions and comparable contractions to arginine vasopressin and K+-induced depolarization. Acetylcholine-induced vasorelaxation and endothelial NO synthase expression are increased in colon cancer feed arteries compared with normal colon arteries, whereas vasorelaxation to exogenous NO donors is unaffected. In congruence, the differences in vasorelaxant and vasocontractile function between colon cancer feed arteries and normal colon arteries decrease after NO synthase inhibition. Rhythmic oscillations in vascular tone, known as vasomotion, are of lower amplitude but similar frequency in colon cancer feed arteries compared with normal colon arteries. In conclusion, higher NO synthase expression and elevated NO signaling amplify vasorelaxation and attenuate vasocontraction of human colon cancer feed arteries. We propose that enhanced endothelial function augments tumor perfusion and represents a potential therapeutic target. NEW & NOTEWORTHY Local vascular resistance influences tumor perfusion. Arteries supplying human colonic adenocarcinomas show enhanced vasorelaxation and reduced vasocontraction mainly due to elevated nitric oxide-mediated signaling. Rhythmic oscillations in tone, known as vasomotion, are attenuated in colon cancer feed arteries.

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