Back

Deamidated TPI is an efficacious target for cell-selective therapy in triple-negative breast cancer

Enriquez-Flores, S.; Flores-Lopez, L. A.; de la Mora-de la Mora, I.; Garcia-Torres, I.; Gracia-Mora, I.; Gutierrez-Castrellon, P.; Fernandez-Lainez, C.; Martinez-Perez, Y.; Olaya-Vargas, A.; Lopez-Velazquez, G.

2021-11-11 cancer biology
10.1101/2021.11.09.467888 bioRxiv
Show abstract

Human TPI (HsTPI) is a central and essential glycolytic enzyme for energy supply and is overexpressed in cancer cells. Here, we investigated HsTPI as a potential target for inducing cell death in triple-hormone receptor-negative breast cancer, which is highly dependent on glycolysis, and therapies for its treatment are limited. We found endogenous accumulation of deamidated HsTPI in human breast cancer cells, which might be caused by the lower activity of the HsTPI-degrading caspase-1 in breast cancer cells. In silico and in vitro analyses of deamidated HsTPI demonstrated the efficacy of thiol-reactive drugs in blocking enzyme activity. The cancer cells were selectively programmed to undergo apoptosis with thiol-reactive drugs by inducing the production of methylglyoxal (MGO) and advanced glycation-end products (AGEs). In vivo in mice, the thiol-reactive drug effectively inhibited the growth of human tumors by targeting HsTPI as underlying mechanism. Our findings demonstrate deamidated HsTPI as a novel target to develop therapeutic strategies for treating cancers and other pathologies in which this post-translationally modified protein accumulates.

Matching journals

The top 10 journals account for 50% of the predicted probability mass.

1
Free Radical Biology and Medicine
○ 36 papers in training set
Top 0.1%
9.6%
Similar papers in this journal
2
International Journal of Molecular Sciences
○ 494 papers in training set
Top 0.4%
8.7%
Similar papers in this journal
3
PLOS ONE
● 5266 papers in training set
Top 24%
6.6%
Similar papers in this journal
4
Molecules
○ 39 papers in training set
Top 0.1%
4.7%
Similar papers in this journal
5
Cell Death & Disease
147 papers in training set
Top 0.5%
4.7%
6
Biochemical Journal
● 91 papers in training set
Top 0.2%
4.2%
7
Redox Biology
○ 70 papers in training set
Top 0.3%
3.9%
8
Biochemical Pharmacology
○ 20 papers in training set
Top 0.1%
3.3%
9
Biomolecules
○ 100 papers in training set
Top 0.4%
3.1%
10
International Journal of Biological Macromolecules
○ 76 papers in training set
Top 0.5%
2.7%
50% of probability mass above
11
Pharmaceuticals
○ 34 papers in training set
Top 0.2%
2.7%
12
Scientific Reports
○ 3612 papers in training set
Top 38%
2.7%
13
Biomedicine & Pharmacotherapy
○ 42 papers in training set
Top 0.4%
2.4%
14
Aging
○ 75 papers in training set
Top 0.6%
2.3%
15
eLife
● 5828 papers in training set
Top 46%
2.1%
16
Biomedicines
○ 67 papers in training set
Top 0.8%
2.1%
17
Molecular Oncology
○ 55 papers in training set
Top 0.5%
2.1%
18
Cancers
○ 213 papers in training set
Top 3%
1.7%
19
The FEBS Journal
○ 93 papers in training set
Top 0.8%
1.7%
20
Heliyon
○ 152 papers in training set
Top 6%
1.1%
21
Biochimica et Biophysica Acta (BBA) - Molecular Cell Research
○ 29 papers in training set
Top 0.4%
1.1%
22
Biochemistry and Biophysics Reports
○ 30 papers in training set
Top 0.8%
1.1%
23
Cancer Letters
○ 35 papers in training set
Top 0.9%
1.1%
24
Frontiers in Oncology
○ 103 papers in training set
Top 3%
1.1%
25
Cells
○ 249 papers in training set
Top 5%
1.1%
26
Journal of Biological Chemistry
○ 690 papers in training set
Top 8%
1.0%
27
Cellular and Molecular Life Sciences
○ 96 papers in training set
Top 2%
1.0%
28
Life Sciences
○ 27 papers in training set
Top 1%
0.9%
29
Biochimica et Biophysica Acta (BBA) - General Subjects
○ 18 papers in training set
Top 0.4%
0.8%
30
FEBS Open Bio
○ 31 papers in training set
Top 0.9%
0.8%

"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.