scholarly journals Metastatic colon cancer cell populations contain more cancer stem-like cells with a higher susceptibility to natural killer cell-mediated lysis compared with primary colon cancer cells

2015 ◽  
Vol 9 (4) ◽  
pp. 1641-1646 ◽  
Author(s):  
GA RIM KIM ◽  
GA-HEE HA ◽  
JAE-HO BAE ◽  
SAE-OCK OH ◽  
SUN-HEE KIM ◽  
...  
Author(s):  
Margalida Torrens-Mas ◽  
Marina Alorda-Clara ◽  
Maria Martínez-Vigara ◽  
Pilar Roca ◽  
Jorge Sastre-Serra ◽  
...  

2013 ◽  
Author(s):  
Martin Lange ◽  
Dirk Schumacher ◽  
Thomas Hauling ◽  
Christian Regenbrecht ◽  
Oliver Politz ◽  
...  

2021 ◽  
Vol 12 (11) ◽  
Author(s):  
Li-hao Zhao ◽  
Quan Li ◽  
Zhi-Jun Huang ◽  
Mi-Xue Sun ◽  
Jing-jing Lu ◽  
...  

AbstractColorectal cancer (CRC) is the second common cause of cancer-related human mortalities. Dysregulation of histone 3 (H3) methylation could lead to transcriptional activation of multiple oncogenes, which is closely associated with CRC tumorigenesis and progression. Nuclear receptor-binding SET Domain protein 2 (NSD2) is a key histone methyltransferase catalyzing histone H3 lysine 36 dimethylation (H3K36me2). Its expression, the potential functions, and molecular mechanisms in CRC are studied here. Gene Expression Profiling Interactive Analysis (GEPIA) bioinformatics results showed that the NSD2 mRNA expression is elevated in both colon cancers and rectal cancers. Furthermore, NSD2 mRNA and protein expression levels in local colon cancer tissues are significantly higher than those in matched surrounding normal tissues. In primary human colon cancer cells and established CRC cell lines, shRNA-induced silencing or CRISPR/Cas9-induced knockout of NSD2 inhibited cell viability, proliferation, cell cycle progression, migration, and invasion. Furthermore, NSD2 shRNA or knockout induced mitochondrial depolarization, DNA damage, and apoptosis in the primary and established CRC cells. Contrarily, ectopic NSD2 overexpression in primary colon cancer cells further enhanced cell proliferation, migration, and invasion. H3K36me2, expressions of multiple oncogenes (ADAM9, EGFR, Sox2, Bcl-2, SYK, and MET) and Akt activation were significantly decreased after NSD2 silencing or knockout in primary colon cancer cells. Their levels were however increased after ectopic NSD2 overexpression. A catalytic inactive NSD2 (Y1179A) also inhibited H3K36me2, multiple oncogenes expression, and Akt activation, as well as cell proliferation and migration in primary colon cancer cells. In vivo, intratumoral injection of adeno-associated virus (AAV)-packed NSD2 shRNA largely inhibited primary colon cancer cell xenograft growth in nude mice. Together, NSD2 exerted oncogenic functions in CRC and could be a promising therapeutic target.


1993 ◽  
Vol 11 (3) ◽  
pp. 291-298 ◽  
Author(s):  
Bozidar Djordjevic ◽  
Christopher S. Lange ◽  
Ronald R. Allison ◽  
Marvin Rotman

2010 ◽  
Vol 31 (8) ◽  
pp. 1376-1380 ◽  
Author(s):  
Y. K. Wang ◽  
Y. L. Zhu ◽  
F. M. Qiu ◽  
T. Zhang ◽  
Z. G. Chen ◽  
...  

2008 ◽  
Vol 417 (1) ◽  
pp. 379-389 ◽  
Author(s):  
Muthusamy Thangaraju ◽  
Kristina N. Carswell ◽  
Puttur D. Prasad ◽  
Vadivel Ganapathy

Human colon cancer cells and primary colon cancer silence the gene coding for LDH (lactate dehydrogenase)-B and up-regulate the gene coding for LDH-A, resulting in effective conversion of pyruvate into lactate. This is associated with markedly reduced levels of pyruvate in cancer cells compared with non-malignant cells. The silencing of LDH-B in cancer cells occurs via DNA methylation, with involvement of the DNMTs (DNA methyltransferases) DNMT1 and DNMT3b. Colon cancer is also associated with the expression of pyruvate kinase M2, a splice variant with low catalytic activity. We have shown recently that pyruvate is an inhibitor of HDACs (histone deacetylases). Here we show that pyruvate is a specific inhibitor of HDAC1 and HDAC3. Lactate has no effect on any of the HDACs examined. Colon cancer cells exhibit increased HDAC activity compared with non-malignant cells. HDAC1 and HDAC3 are up-regulated in colon cancer cells and in primary colon cancer, and siRNA (small interfering RNA)-mediated silencing of HDAC1 and HDAC3 in colon cancer cells induces apoptosis. Colon cancer cells silence SLC5A8, the gene coding for a Na+-coupled pyruvate transporter. Heterologous expression of SLC5A8 in the human colon cancer cell line SW480 leads to inhibition of HDAC activity when cultured in the presence of pyruvate. This process is associated with an increase in intracellular levels of pyruvate, increase in the acetylation status of histone H4, and enhanced cell death. These studies show that cancer cells effectively maintain low levels of pyruvate to prevent inhibition of HDAC1/HDAC3 and thereby to evade cell death.


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