Overexpression of ubiquitous mitochondrial creatine kinase (uMtCK) accelerates tumor growth by inhibiting apoptosis of breast cancer cells and is associated with a poor prognosis in breast cancer patients

Qian, Xiao Long; Li, Ya Qing; Gu, Feng; Liu, Fang Fang; Li, Wei Dong; Zhang, Xin Min; Li, Fu

doi:10.1016/j.bbrc.2012.08.147

Cited by 34 publications

(46 citation statements)

References 24 publications

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“…The current model of mitochondrial interactosome (MI) considers the ATP synthasome and RC complexes together with voltage-dependent anion channel (VDAC) and mitochondrial creatine kinase (MtCK) as components of intracellular energetic units [22]. Even though MI is proven in striated muscles, the functional role of it, together with MtCK, in malignant samples remains controversial [78], but it indicates that both ATP synthasome and RC complexes can form even more complex functional structures.…”

Section: Resultsmentioning

confidence: 99%

Mitochondrial Respiration in Human Colorectal and Breast Cancer Clinical Material Is Regulated Differently

Koit

Shevchuk

Ounpuu

et al. 2017

Oxidative Medicine and Cellular Longevity

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We conducted quantitative cellular respiration analysis on samples taken from human breast cancer (HBC) and human colorectal cancer (HCC) patients. Respiratory capacity is not lost as a result of tumor formation and even though, functionally, complex I in HCC was found to be suppressed, it was not evident on the protein level. Additionally, metabolic control analysis was used to quantify the role of components of mitochondrial interactosome. The main rate-controlling steps in HBC are complex IV and adenine nucleotide transporter, but in HCC, complexes I and III. Our kinetic measurements confirmed previous studies that respiratory chain complexes I and III in HBC and HCC can be assembled into supercomplexes with a possible partial addition from the complex IV pool. Therefore, the kinetic method can be a useful addition in studying supercomplexes in cell lines or human samples. In addition, when results from culture cells were compared to those from clinical samples, clear differences were present, but we also detected two different types of mitochondria within clinical HBC samples, possibly linked to two-compartment metabolism. Taken together, our data show that mitochondrial respiration and regulation of mitochondrial membrane permeability have substantial differences between these two cancer types when compared to each other to their adjacent healthy tissue or to respective cell cultures.

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Section: Resultsmentioning

confidence: 99%

Mitochondrial Respiration in Human Colorectal and Breast Cancer Clinical Material Is Regulated Differently

Koit

Shevchuk

Ounpuu

et al. 2017

Oxidative Medicine and Cellular Longevity

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“…PTTG1, F2RL1) as well as genes related to the transfer of high energy phosphate from mitochondria, potentially related to the failure to eliminate cancer cells via apoptosis (e.g. CKMT1A) [48, 49]. …”

Section: Discussionmentioning

confidence: 99%

Genomic characterization of liver metastases from colorectal cancer patients

et al. 2016

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Metastatic dissemination is the most frequent cause of death of sporadic colorectal cancer (sCRC) patients. Genomic abnormalities which are potentially characteristic of such advanced stages of the disease are complex and so far, they have been poorly described and only partially understood. We evaluated the molecular heterogeneity of sCRC tumors based on simultaneous assessment of the overall GEP of both coding mRNA and non-coding RNA genes in primary sCRC tumor samples from 23 consecutive patients and their paired liver metastases. Liver metastases from the sCRC patients analyzed, systematically showed deregulated transcripts of those genes identified as also deregulated in their paired primary colorectal carcinomas. However, some transcripts were found to be specifically deregulated in liver metastases (vs. non-tumoral colorectal tissues) while expressed at normal levels in their primary tumors, reflecting either an increased genomic instability of metastatic cells or theiradaption to the liver microenvironment. Newly deregulated metastatic transcripts included overexpression of APOA1, HRG, UGT2B4, RBP4 and ADH4 mRNAS and the miR-3180-3p, miR-3197, miR-3178, miR-4793 and miR-4440 miRNAs, together with decreased expression of the IGKV1-39, IGKC, IGKV1-27, FABP4 and MYLK mRNAS and the miR-363, miR-1, miR-143, miR-27b and miR-28-5p miRNAs. Canonical pathways found to be specifically deregulated in liver metastatic samples included multiple genes related with intercellular adhesion and the metastatic processes (e.g., IGF1R, PIK3CA, PTEN and EGFR), endocytosis (e.g., the PDGFRA, SMAD2, ERBB3, PML and FGFR2), and the cell cycle (e.g., SMAD2, CCND2, E2F5 and MYC). Our results also highlighted the activation of genes associated with the TGFβ signaling pathway, -e.g. RHOA, SMAD2, SMAD4, SMAD5, SMAD6, BMPR1A, SMAD7 and MYC-, which thereby emerge as candidate genes to play an important role in CRC tumor metastasis.

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“…Mitochondria are key organelles for energy production including glucose metabolism and oxidative phosphorylation with a critical role in cell survival and apoptosis. Amount and activity of mitochondria may hence play a critical role in tumor initiation and progression [4], and it is not surprising that mutations of mitochondrial genes or alterations of the mitochondrial content have been suggested to play an important role in various cancer types [5-8]. As a consequence, an increasing number of anti-cancer drugs is under development [9-11] targeting mitochondria and associated structures.…”

Section: Introductionmentioning

confidence: 99%

High mitochondria content is associated with prostate cancer disease progression

et al. 2013

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BackgroundMitochondria are suggested to be important organelles for cancer initiation and promotion. This study was designed to evaluate the prognostic value of MTC02, a marker for mitochondrial content, in prostate cancer.MethodsImmunohistochemistry of using an antibody against MTC02 was performed on a tissue microarray (TMA) containing 11,152 prostate cancer specimens. Results were compared to histological phenotype, biochemical recurrence, ERG status and other genomic deletions by using our TMA attached molecular information.ResultsTumor cells showed stronger MTC02 expression than normal prostate epithelium. MTC02 immunostaining was found in 96.5% of 8,412 analyzable prostate cancers, including 15.4% tumors with weak, 34.6% with moderate, and 46.5% with strong expression. MTC02 expression was associated with advanced pathological tumor stage, high Gleason score, nodal metastases (p < 0.0001 each), positive surgical margins (p = 0.0005), and early PSA recurrence (p < 0.0001) if all cancers were jointly analyzed. Tumors harboring ERG fusion showed higher expression levels than those without (p < 0.0001). In ERG negative prostate cancers, strong MTC02 immunostaining was linked to deletions of PTEN, 6q15, 5q21, and early biochemical recurrence (p < 0.0001 each). Moreover, multiple scenarios of multivariate analyses suggested an independent association of MTC02 with prognosis in preoperative settings.ConclusionsOur study demonstrates high-level MTC02 expression in ERG negative prostate cancers harboring deletions of PTEN, 6q15, and 5q21. Additionally, increased MTC02 expression is a strong predictor of poor clinical outcome in ERG negative cancers, highlighting a potentially important role of elevated mitochondrial content for prostate cancer cell biology.

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Overexpression of ubiquitous mitochondrial creatine kinase (uMtCK) accelerates tumor growth by inhibiting apoptosis of breast cancer cells and is associated with a poor prognosis in breast cancer patients

Cited by 34 publications

References 24 publications

Mitochondrial Respiration in Human Colorectal and Breast Cancer Clinical Material Is Regulated Differently

Mitochondrial Respiration in Human Colorectal and Breast Cancer Clinical Material Is Regulated Differently

Genomic characterization of liver metastases from colorectal cancer patients

High mitochondria content is associated with prostate cancer disease progression

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