Differential Expression of ADP/ATP Carriers as a Biomarker of Metabolic Remodeling and Survival in Kidney Cancers

被引：17

作者：

Trisolini, Lucia ^{[1
]}

Laera, Luna ^{[1
]}

Favia, Maria ^{[1
]}

Muscella, Antonella ^{[2
]}

Castegna, Alessandra ^{[1
]}

Pesce, Vito ^{[1
]}

Guerra, Lorenzo ^{[1
]}

De Grassi, Anna ^{[1
,3
]}

Volpicella, Mariateresa ^{[1
]}

Pierri, Ciro Leonardo ^{[1
,3
]}

机构：

[1] Univ Aldo Moro Bari, Dept Biosci, Biotechnol, Biopharmaceut, Via E Orabona 4, I-70125 Bari, Italy

[2] Univ Salento, Dipartimento Sci & Tecnol Biol & Ambientali DiSTe, I-73100 Lecce, Italy

[3] Univ Aldo Moro Bari, BROWSer Srl, Dept Biosci, Biotechnol,Biopharmaceut, Via E Orabona 4, I-70126 Bari, Italy

来源：

BIOMOLECULES | 2021年 / 11卷 / 01期

关键词：

ADP; ATP carriers (AACs); SLC25A family; mitochondrial apoptosis; mitochondrial permeability transition pore (mPTP); kidney cancer; biomarkers of survival; biomarkers of metabolic remodeling; GENE-EXPRESSION; MITOCHONDRIAL METABOLISM; OXIDATIVE STRESS; ATP SYNTHASE; CELL-DEATH; IN-VIVO; APOPTOSIS; TRANSPORT; IDENTIFICATION; COMPLEX;

D O I：

10.3390/biom11010038

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

ADP/ATP carriers (AACs) are mitochondrial transport proteins playing a strategic role in maintaining the respiratory chain activity, fueling the cell with ATP, and also regulating mitochondrial apoptosis. To understand if AACs might represent a new molecular target for cancer treatment, we evaluated AAC expression levels in cancer/normal tissue pairs available on the Tissue Cancer Genome Atlas database (TCGA), observing that AACs are dysregulated in most of the available samples. It was observed that at least two AACs showed a significant differential expression in all the available kidney cancer/normal tissue pairs. Thus, we investigated AAC expression in the corresponding kidney non-cancer (HK2)/cancer (RCC-Shaw and CaKi-1) cell lines, grown in complete medium or serum starvation, for investigating how metabolic alteration induced by different growth conditions might influence AAC expression and resistance to mitochondrial apoptosis initiators, such as "staurosporine" or the AAC highly selective inhibitor "carboxyatractyloside". Our analyses showed that AAC2 and AAC3 transcripts are more expressed than AAC1 in all the investigated kidney cell lines grown in complete medium, whereas serum starvation causes an increase of at least two AAC transcripts in kidney cancer cell lines compared to non-cancer cells. However, the total AAC protein content is decreased in the investigated cancer cell lines, above all in the serum-free medium. The observed decrease in AAC protein content might be responsible for the decrease of OXPHOS activity and for the observed lowered sensitivity to mitochondrial apoptosis induced by staurosporine or carboxyatractyloside. Notably, the cumulative probability of the survival of kidney cancer patients seriously decreases with the decrease of AAC1 expression in KIRC and KIRP tissues making AAC1 a possible new biomarker of metabolic remodeling and survival in kidney cancers.

引用

页码：1 / 16

页数：16

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