Choline Kinase Alpha and Hexokinase-2 Protein Expression in Hepatocellular Carcinoma: Association with Survival

Kwee, Sandi A.; Hernandez, Brenda Y.; Chan, Owen; Wong, Linda L.

doi:10.1371/journal.pone.0046591

Cited by 93 publications

(97 citation statements)

References 40 publications

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“…Indeed, HK-II expression levels are closely associated with tumor grade and mortality in hepatocellular carcinoma. 29 Although in normal brain and low-grade gliomas HK-I is the predominant isoform, HK-II is highly upregulated in human glioblastoma multiforme 30 and poor prognosis is associated with upregulation of HK-II in human brain metastases of breast cancer. 31 Thus HK-II upregulation is considered a consequence of metabolic re-programming in cancer.…”

Section: Hexokinase II In Metabolismmentioning

confidence: 99%

Hexokinase II integrates energy metabolism and cellular protection: Akting on mitochondria and TORCing to autophagy

2014

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Accumulating evidence reveals that metabolic and cell survival pathways are closely related, sharing common signaling molecules. Hexokinase catalyzes the phosphorylation of glucose, the rate-limiting first step of glycolysis. Hexokinase II (HK-II) is a predominant isoform in insulin-sensitive tissues such as heart, skeletal muscle, and adipose tissues. It is also upregulated in many types of tumors associated with enhanced aerobic glycolysis in tumor cells, the Warburg effect. In addition to the fundamental role in glycolysis, HK-II is increasingly recognized as a component of a survival signaling nexus. This review summarizes recent advances in understanding the protective role of HK-II, controlling cellular growth, preventing mitochondrial death pathway and enhancing autophagy, with a particular focus on the interaction between HK-II and Akt/mTOR pathway to integrate metabolic status with the control of cell survival.

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Section: Hexokinase II In Metabolismmentioning

confidence: 99%

Hexokinase II integrates energy metabolism and cellular protection: Akting on mitochondria and TORCing to autophagy

2014

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“…Personalized therapies based on individual molecular profiles have proven more efficient, by reducing side effects and improving clinical outcomes (39). ChoKa expression levels have been reported as an independent prognostic biomarker for early-stage NSCLC (40) and for hepatocarcinomas (41). Thus, taking into consideration the status of ChoKa expression levels in the tumor may represent significant and valuable information to treat patients with this novel family of therapeutic tools.…”

Section: Discussionmentioning

confidence: 99%

Preclinical Characterization of RSM-932A, a Novel Anticancer Drug Targeting the Human Choline Kinase Alpha, an Enzyme Involved in Increased Lipid Metabolism of Cancer Cells

Lacal

Campos

2015

Molecular Cancer Therapeutics

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Choline kinase a (CHKA; here designated as ChoKa) is the first enzyme in the CDP-choline pathway, implicated in phospholipids metabolism. It is overexpressed in several human tumors such as breast, lung, bladder, colorectal, prostate, ovary, and liver. The overexpression of ChoKa has oncogenic potential and synergizes with other known oncogenes. It has been proposed as a novel cancer drug target with a distinct mechanism of action. We have generated a set of ChoKa inhibitors with potent in vitro antiproliferative and in vivo antitumoral activity against human xenografts in mice, showing high efficacy with low toxicity profiles. Among these inhibitors, RSM-932A has been chosen for further clinical development due to its potent antiproliferative activity in vitro against a large variety of tumorderived cell lines, a potent in vivo anticancer activity, and lack of toxicity at the effective doses. Here, we provide the preclinical evidence to support the use of RSM-932A as a good candidate to be tested in clinical trials as the "first in humans" drug targeting ChoKa.

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“…Other studies focused on cancer types responsible for an increasing proportion of cancer deaths, including pancreas (8, 21, 35, 36) and liver cancer (19, 22, 33). Other cancer types of interest were lymphomas (11–13, 26, 28); cancers of the ovaries (25), oral cavity, and pharynx (14, 31); and cervical cancer (20).…”

Section: Resultsmentioning

confidence: 99%

“…FFPE cores also were used to construct tissue microarrays (TMA) (8, 9, 18, 21, 22, 24, 32, 35, 36) and multiple tumor block arrays (26, 28). In one study, FFPE tissues were used for pathology review, and frozen normal tissues were used for DNA methylation studies (33).…”

Section: Resultsmentioning

confidence: 99%

“…Several studies reported cancer subtype distributions across racial and ethnic populations (9, 12–14, 17, 18, 20–22, 24, 26, 35–38). Biospecimens also were used to study molecular subtype distributions in the populations for cancer of the breast (9) and colon and rectum (30), and for non-Hodgkin lymphoma (11–13), including subtypes of diffuse large B-cell lymphoma (28) and Burkitt lymphoma (26).…”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

SEER Cancer Registry Biospecimen Research: Yesterday and Tomorrow

Altekruse

Rosenfeld

Carrick

et al. 2014

Cancer Epidemiology, Biomarkers &Amp; Prevention

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The National Cancer Institute's (NCI) Surveillance, Epidemiology, and End Results (SEER) registries have been a source of biospecimens for cancer research for decades. Recently, registry-based biospecimen studies have become more practical, with the expansion of electronic networks for pathology and medical record reporting. Formalin-fixed paraffin-embedded specimens are now used for next-generation sequencing and other molecular techniques. These developments create new opportunities for SEER biospecimen research. We evaluated 31 research articles published during 2005–2013 based on author confirmation that these studies involved linkage of SEER data to biospecimens. Rather than providing an exhaustive review of all possible articles, our intent was to indicate the breadth of research made possible by such a resource. We also summarize responses to a 2012 questionnaire that was broadly distributed to the NCI intra- and extramural biospecimen research community. This included responses from 30 investigators who had used SEER biospecimens in their research. The survey was not intended to be a systematic sample, but instead to provide anecdotal insight on strengths, limitations, and the future of SEER biospecimen research. Identified strengths of this research resource include biospecimen availability, cost, and annotation of data, including demographic information, stage, and survival. Shortcomings include limited annotation of clinical attributes such as detailed chemotherapy history and recurrence, and timeliness of turnaround following biospecimen requests. A review of selected SEER biospecimen articles, investigator feedback, and technological advances reinforced our view that SEER biospecimen resources should be developed. This would advance cancer biology, etiology, and personalized therapy research.

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Choline Kinase Alpha and Hexokinase-2 Protein Expression in Hepatocellular Carcinoma: Association with Survival

Cited by 93 publications

References 40 publications

Hexokinase II integrates energy metabolism and cellular protection: Akting on mitochondria and TORCing to autophagy

Hexokinase II integrates energy metabolism and cellular protection: Akting on mitochondria and TORCing to autophagy

Preclinical Characterization of RSM-932A, a Novel Anticancer Drug Targeting the Human Choline Kinase Alpha, an Enzyme Involved in Increased Lipid Metabolism of Cancer Cells

SEER Cancer Registry Biospecimen Research: Yesterday and Tomorrow

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