| Title |
Positive feedback between oncogenic KRAS and HIF-1α confers drug resistance in colorectal cancer
|
|---|---|
| Published in |
OncoTargets and therapy, May 2015
|
| DOI | 10.2147/ott.s80017 |
| Pubmed ID | |
| Authors |
Yanzhao Wang, Fuming Lei, Wanshui Rong, Qingmin Zeng, Wenbing Sun |
| Abstract |
Approximately 30%-50% of colorectal cancers (CRCs) harbor the somatic mutated KRAS gene. KRAS G12V, one of the most common KRAS mutations in CRCs, is linked to increased tumor aggressiveness, less response to anti-epidermal growth factor receptor (EGFR) therapy, and poor survival rate. In this study, we sought to determine whether resistance to EGFR inhibitors in colorectal cancer cells harboring KRAS G12V mutation is associated with hypoxia. Our data indicated that HIF-1α was induced by KRAS G12V signaling at transcription level. Hypoxia or HIF-1α overexpression could increase KRAS G12V activity. Therefore, a positive feedback between hypoxia and KRAS G12V activation was formed. Cetuximab, an EGFR inhibitor, which has a minor effect on KRAS-mutant CRCs, could effectively inhibit the proliferation of CRC cells harboring KRAS G12V mutation when combined with HIF-1α inhibitor PX-478. Our data indicated that hypoxia was involved in resistance to anti-EGFR therapy, and a combination therapy might be necessary for CRC patients with KRAS mutation. |
X Demographics
The data shown below were collected from the profile of 1 X user who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 1 | 100% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 1 | 100% |
Mendeley readers
The data shown below were compiled from readership statistics for 42 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Spain | 1 | 2% |
| Unknown | 41 | 98% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Ph. D. Student | 12 | 29% |
| Researcher | 4 | 10% |
| Student > Bachelor | 4 | 10% |
| Student > Doctoral Student | 3 | 7% |
| Student > Postgraduate | 3 | 7% |
| Other | 7 | 17% |
| Unknown | 9 | 21% |
| Readers by discipline | Count | As % |
|---|---|---|
| Biochemistry, Genetics and Molecular Biology | 16 | 38% |
| Medicine and Dentistry | 4 | 10% |
| Agricultural and Biological Sciences | 4 | 10% |
| Chemical Engineering | 2 | 5% |
| Pharmacology, Toxicology and Pharmaceutical Science | 2 | 5% |
| Other | 7 | 17% |
| Unknown | 7 | 17% |
Attention Score in Context
This research output has an Altmetric Attention Score of 1. 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 11 June 2015.
All research outputs
#20,656,161
of 25,373,627 outputs
Outputs from OncoTargets and therapy
#1,597
of 3,016 outputs
Outputs of similar age
#206,515
of 278,920 outputs
Outputs of similar age from OncoTargets and therapy
#31
of 49 outputs
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