Overexpression of CHKA contributes to tumor progression and metastasis and predicts poor prognosis in colorectal carcinoma

Hu, Liang; Wang, Ruo–Yu; Cai, Jian; Feng, Dan; Yang, Guosheng; Xu, Qingguo; Zhai, Yan-Xia; Zhou, Weiping; Cai, Qing-Qing

doi:10.18632/oncotarget.11433

Cited by 25 publications

(24 citation statements)

References 62 publications

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“…However, only EDI3 affected cell migration, indicating that this ratio is not predictive of migratory capacity. Interestingly, our findings differ from those of previous studies where silencing CHKA decreased motility and invasion (9)(10)(11)(12). In two studies (9,10), the authors reported reduced proliferation, but no direct effect on apoptosis, or on MAPK and PI3K/Akt signaling pathways, as published by others after CHKA inhibition in other cell lines (30)(31)(32)(33).…”

Section: Discussioncontrasting

confidence: 99%

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Glycerol-3-phosphate Acyltransferase 1 Promotes Tumor Cell Migration and Poor Survival in Ovarian Carcinoma

et al. 2017

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Glycerophosphodiesterase EDI3 (GPCPD1; GDE5; GDPD6) has been suggested to promote cell migration, adhesion, and spreading, but its mechanisms of action remain uncertain. In this study, we targeted the glycerol-3-phosphate acyltransferase GPAM along with choline kinase-a (CHKA), the enzymes that catabolize the products of EDI3 to determine which downstream pathway is relevant for migration. Our results clearly showed that GPAM influenced cell migration via the signaling lipid lysophosphatidic acid (LPA), linking it with GPAM to cell migration. Analysis of GPAM expression in different cancer types revealed a significant association between high GPAM expression and reduced overall survival in ovarian cancer. Silencing GPAM in ovarian cancer cells decreased cell migration and reduced the growth of tumor xenografts. In contrast to these observations, manipulating CHKA did not influence cell migration in the same set of cell lines. Overall, our findings show how GPAM influences intracellular LPA levels to promote cell migration and tumor growth.

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Section: Discussioncontrasting

confidence: 99%

“…1A), respectively. CHKA has been previously linked to migration (9)(10)(11)(12); however, a role for GPAM in this process has never been described.…”

Section: ) To Elucidate Edi3mentioning

confidence: 99%

Glycerol-3-phosphate Acyltransferase 1 Promotes Tumor Cell Migration and Poor Survival in Ovarian Carcinoma

et al. 2017

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“…On evaluating the integration sites in our study, breakpoints of viral integration involved exonic, intronic and intergenic sites in the human genome. The exonic and intronic viral integration created fusions with 6 different human genes: TSTD1, CHKA, MUC6, MACROD2, CAPN1, and SCAPER, 5 of which have been implicated in cancers [30][31][32][33][34][35]. SCAPER is a Cyclin A substrate that forms a complex with it to regulate its kinase activity and may have a role in G1/S and G2/M phases of cell cycle [36].…”

Section: Discussionmentioning

confidence: 99%

Polyoma virus-associated carcinomas of the urologic tract: a clinicopathologic and molecular study

Sirohi

Vaske²,

Sanborn³

et al. 2018

Modern Pathology

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In recent years, there has been increased interest in carcinomas of the urologic tract, that demonstrate association with the polyoma virus BK arising in immunosuppressed individuals, though the nature of this association is uncertain. To begin to understand this phenomenon, we reviewed the clinical, morphological, and immunohistochemical features of 11 carcinomas of the urologic tract, mainly urothelial (N = 9) and collecting duct carcinomas (N = 2), occurring during immunosuppression, and expressing polyoma virus T-antigen by immunohistochemistry. These were compared to a control group of carcinomas (N = 8), also arising during immunosuppression, but without T-antigen expression. A subset of both groups were also studied by hybrid capture-based DNA sequencing, probing not only for 479 cancer-related human genes, but also for polyoma and other viral sequences. Polyoma T-antigen-expressing tumors arose in 7 males and 4 females, at a median age of 66, and were aggressive, high-grade tumors with more than 1 variant morphologic pattern identified in 81% of cases, and a majority (73%) presenting at high stage category (>pT3). Diffuse polyoma T-antigen staining was seen in 91% of cases, with co-localization of aberrant p53 staining in 89%. Sequencing detected a lower number of deleterious mutations among T-antigen-expressing cases (average 1.62; 1/8 with TP53 mutation) compared to control cases (average 3.5, 2/4 with TP53 mutation). Only BK virus was detected with clonal integration and breakpoints randomly distributed across the human and viral genomes in 5/5 of the polyoma T-antigen-expressing carcinomas, and in none of the controls (0/4). In summary, these findings identify aggressive clinicopathologic features of polyoma T-antigen-expressing carcinomas, document BK as the strain involved, and associate BK viral integration with T-antigen expression and p53 aberrancy. While the apparent randomness of viral insertion sites is functionally unclear, the differing rates of mutations between T-antigen-expressing and control cases is intriguing.

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“…Существует гипотеза о влиянии ХКα на пролиферацию и трансформацию клеток путем регулирования смены фаз клеточного цикла G1-S и сигналов к апоптозу [11]. Гиперэкспрессия ХКα зафиксированан в тканях опухолей молочной железы, легкого, толстой кишки, мочевого пузыря и предстательной железы человека, при этом в неизмененных тканях экспрессия фермента этой изоформы была слабой [11][12][13][14].…”

Section: обоснованиеunclassified

“…В то же время оценка выраженности экспрессии ХКα с помощью иммуногистохимического (ИГХ) метода зарекомендовала себя при анализе образцов тканей опухолей молочной железы, легких и предстательной железы [21][22]. Ряд исследователей связывают степень и характер экспрессии ХКα с прогнозом заболевания [12,14,16]. Большинство из них склонны расценивать гиперэкспрессию ХКα, как неблагоприятный прогностический фактор [12,14,23].…”

Section: обоснованиеunclassified

Evaluation of the metabolism properties of choline kinase alpha in neoplasms of the parathyroid glands. A pilot study

et al. 2019

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BACKGROUND: Primary hyperparathyroidism (PHPT) is a widespread endocrine disease characterized by excessive production of parathyroid hormone (PTH) due to parathyroid gland hyperplasia (PGH) or tumor lesions (adenoma or cancer of the parathyroid gland (PG) in 80% and 15% of cases respectively). Choline kinase alpha (XK) overexpression is described in tumors of different localization, but there is no data on its expression in PG tumors. AIMS: To study the character of XK expression in PG neoplasms and its relationship with clinical, laboratory, and visualization characteristics (positron emission tomography combined with computed tomography (PET/CT) with 18Ffluorocholine (18FFC)). MATERIALS AND METHODS: The material for the study was based on tissue samples from 10 patients of 3470 years old (Me = 61.5; [48; 66]), with a laboratoryconfirmed diagnosis of PHT. An immunohistochemical study (IHC) was carried out on materials from 2 patients with hyperplasia of the main cells, from 5 patients with adenoma of PG, from 1 patient with atypical adenoma and 1 with carcinoma of PG; in 1 case the metastasis of cancer of the neck with lymph node was examined. RESULTS: The expression of XK is spotted in all types of PG cells (chief cells: active and inactive forms), transitional forms between the chief cells and oxyphil; oxyphil cells, but it was most intense in active chief cells. The expression of XK was observed in neoplasms of PG of various degrees of malignancy. In the most numerous group of PG formations with a favorable prognosis (11 samples from 7 patients), no statistically significant correlation (p 0.05) was obtained between the intensity expression of the XK, of the PTH and the proliferative activity index Ki67, the level of radiopharmaceutical accumulation in PET/CT with 18FFC (SUVmax) and laboratory data (PTH, Ca, Ca++). CONCLUSIONS: In the majority of investigated cases, moderate and intensive expression of the XK was detected in PG cells. A small amount of studied cases does not allow us to identify the connection between the intensity of XK expression and the malignant potential for the formation of PG.

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Overexpression of CHKA contributes to tumor progression and metastasis and predicts poor prognosis in colorectal carcinoma

Cited by 25 publications

References 62 publications

Glycerol-3-phosphate Acyltransferase 1 Promotes Tumor Cell Migration and Poor Survival in Ovarian Carcinoma

Glycerol-3-phosphate Acyltransferase 1 Promotes Tumor Cell Migration and Poor Survival in Ovarian Carcinoma

Polyoma virus-associated carcinomas of the urologic tract: a clinicopathologic and molecular study

Evaluation of the metabolism properties of choline kinase alpha in neoplasms of the parathyroid glands. A pilot study

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