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Inhibition of AKT1 signaling promotes invasion and metastasis of non-small cell lung cancer cells with K-RAS or EGFR mutations

Overview of attention for article published in Scientific Reports, August 2017
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Title
Inhibition of AKT1 signaling promotes invasion and metastasis of non-small cell lung cancer cells with K-RAS or EGFR mutations
Published in
Scientific Reports, August 2017
DOI 10.1038/s41598-017-06128-9
Pubmed ID
Authors

Guanhua Rao, Mariaelena Pierobon, In-Kyu Kim, Wei-Hsun Hsu, Jianghong Deng, Yong-Wha Moon, Emanuel F. Petricoin, Yu-Wen Zhang, Yisong Wang, Giuseppe Giaccone

Abstract

Accumulating evidence supports a role of the PI3K-AKT pathway in the regulation of cell motility, invasion and metastasis. AKT activation is known to promote metastasis, however under certain circumstances, it also shows an inhibitory activity on metastatic processes, and the cause of such conflicting results is largely unclear. Here we found that AKT1 is an important regulator of metastasis and down-regulation of its activity is associated with increased metastatic potential of A549 cells. Inhibition of AKT1 enhanced migration and invasion in KRAS- or EGFR-mutant non-small cell lung cancer (NSCLC) cells. The allosteric AKT inhibitor MK-2206 promoted metastasis of KRAS-mutated A549 cells in vivo. We next identified that the phosphorylation of Myristoylated alanine-rich C-kinase substrate (MARCKS) and LAMC2 protein level were increased with AKT1 inhibition, and MARCKS or LAMC2 knockdown abrogated migration and invasion induced by AKT1 inhibition. This study unravels an anti-metastatic role of AKT1 in the NSCLC cells with KRAS or EGFR mutations, and establishes an AKT1-MARCKS-LAMC2 feedback loop in this regulation.

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The data shown below were collected from the profiles of 2 X users who shared this research output. Click here to find out more about how the information was compiled.
Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 52 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 52 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 10 19%
Researcher 8 15%
Student > Master 7 13%
Student > Bachelor 4 8%
Student > Doctoral Student 2 4%
Other 5 10%
Unknown 16 31%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 15 29%
Agricultural and Biological Sciences 7 13%
Medicine and Dentistry 6 12%
Engineering 3 6%
Chemistry 2 4%
Other 2 4%
Unknown 17 33%
Attention Score in Context

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 08 August 2017.
All research outputs
#17,910,703
of 22,996,001 outputs
Outputs from Scientific Reports
#87,760
of 124,150 outputs
Outputs of similar age
#227,604
of 317,441 outputs
Outputs of similar age from Scientific Reports
#3,949
of 6,009 outputs
Altmetric has tracked 22,996,001 research outputs across all sources so far. This one is in the 19th percentile – i.e., 19% of other outputs scored the same or lower than it.
So far Altmetric has tracked 124,150 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 18.2. This one is in the 24th percentile – i.e., 24% of its peers scored the same or lower than it.
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 317,441 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 23rd percentile – i.e., 23% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 6,009 others from the same source and published within six weeks on either side of this one. This one is in the 28th percentile – i.e., 28% of its contemporaries scored the same or lower than it.