| Title |
Targeting colorectal cancer stem cells with inducible caspase-9
|
|---|---|
| Published in |
Apoptosis, January 2012
|
| DOI | 10.1007/s10495-011-0692-z |
| Pubmed ID | |
| Authors |
Kristel Kemper, Hans Rodermond, Selçuk Colak, Catarina Grandela, Jan Paul Medema |
| Abstract |
Colorectal cancer stem cells (CSCs) drive tumor growth and are suggested to initiate distant metastases. Moreover, colon CSCs are reportedly more resistant to conventional chemotherapy, which is in part due to upregulation of anti-apoptotic Bcl-2 family members. To determine whether we could circumvent this apoptotic blockade, we made use of an inducible active caspase-9 (iCasp9) construct to target CSCs. Dimerization of iCasp9 with AP20187 in HCT116 colorectal cancer cells resulted in massive and rapid induction of apoptosis. In contrast to fluorouracil (5-FU)-induced apoptosis, iCasp9-induced apoptosis was independent of the mitochondrial pathway as evidenced by Bax/Bak double deficient HCT116 cells. Dimerizer treatment of colon CSCs transduced with iCasp9 (CSC-iCasp9) also rapidly induced high levels of apoptosis, while these cells were unresponsive to 5-FU in vitro. More importantly, injection of the dimerizer into mice that developed a colon CSC-iCasp9-induced tumor resulted in a strong decrease in tumor size, an increase in tumor cell apoptosis and a clear loss of CD133(+) CSCs. Taken together, our data indicate that dimerization of iCasp9 circumvents the apoptosis block in CSCs, which results in effective tumor regression in vivo. |
Mendeley readers
The data shown below were compiled from readership statistics for 70 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Iran, Islamic Republic of | 1 | 1% |
| Spain | 1 | 1% |
| Portugal | 1 | 1% |
| Luxembourg | 1 | 1% |
| Unknown | 66 | 94% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Ph. D. Student | 22 | 31% |
| Student > Master | 13 | 19% |
| Researcher | 11 | 16% |
| Student > Bachelor | 8 | 11% |
| Student > Doctoral Student | 3 | 4% |
| Other | 10 | 14% |
| Unknown | 3 | 4% |
| Readers by discipline | Count | As % |
|---|---|---|
| Agricultural and Biological Sciences | 32 | 46% |
| Biochemistry, Genetics and Molecular Biology | 19 | 27% |
| Medicine and Dentistry | 7 | 10% |
| Chemistry | 2 | 3% |
| Computer Science | 1 | 1% |
| Other | 3 | 4% |
| Unknown | 6 | 9% |
Attention Score in Context
This research output has an Altmetric Attention Score of 9. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 08 August 2023.
All research outputs
#3,357,725
of 23,253,955 outputs
Outputs from Apoptosis
#35
of 811 outputs
Outputs of similar age
#27,376
of 243,795 outputs
Outputs of similar age from Apoptosis
#2
of 7 outputs
Altmetric has tracked 23,253,955 research outputs across all sources so far. Compared to these this one has done well and is in the 84th percentile: it's in the top 25% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 811 research outputs from this source. They receive a mean Attention Score of 3.6. This one has done particularly well, scoring higher than 93% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 243,795 tracked outputs that were published within six weeks on either side of this one in any source. This one has done well, scoring higher than 87% of its contemporaries.
We're also able to compare this research output to 7 others from the same source and published within six weeks on either side of this one. This one has scored higher than 5 of them.