Expression of the sperm fibrous sheath protein CABYR in human cancers and identification of α-enolase as an interacting partner of CABYR-a

Spaceflight presents a spectrum of stresses very different from those associated with terrestrial conditions. Our previous study (BMC Genom. 15: 659, 2014) integrated the expressions of mRNAs, microRNAs, and proteins and results indicated that microgravity induces an immunosuppressive state that can facilitate opportunistic pathogenic attack. However, the existing data are not sufficient for elucidating the molecular drivers of the given immunosuppressed state. To meet this knowledge gap, we focused on the metabolite profile of spaceflown human cells. Independent studies have attributed cellular energy deficiency as a major cause of compromised immunity of the host, and metabolites that are closely associated with energy production could be a robust signature of atypical energy fluctuation. Our protocol involved inoculation of human endothelial cells in cell culture modules in spaceflight and on the ground concurrently. Ten days later, the cells in space and on the ground were exposed to lipopolysaccharide (LPS), a ubiquitous membrane endotoxin of Gram-negative bacteria. Nucleic acids, proteins, and metabolites were collected 4 and 8 h post-LPS exposure. Untargeted profiling of metabolites was followed by targeted identification of amino acids and knowledge integration with gene expression profiles. Consistent with the past reports associating microgravity with increased energy expenditure, we identified several markers linked to energy deficiency, including various amino acids such as tryptophan, creatinine, dopamine, and glycine, and cofactors such as lactate and pyruvate. The present study revealed a molecular architecture linking energy metabolism and immunodeficiency in microgravity. The energy-deficient condition potentially cascaded into dysregulation of protein metabolism and impairment of host immunity. This project is limited by a small sample size. Although a strict statistical screening was carefully implemented, the present results further emphasize the need for additional studies with larger sample sizes. Validating this hypothesis using an in vivo model is essential to extend the knowledge towards identifying markers of diagnostic and therapeutic value.

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“…A rather extreme consequence could be expected in light of depleted spermidine, which enhances protection against ROS-mediated damage. 57 …”

Section: Discussionmentioning

confidence: 99%

Gene-metabolite profile integration to understand the cause of spaceflight induced immunodeficiency

et al. 2018

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“…Although 1,829 high confidence KRAS PC-Map members (S RF ≥ 0.5) were predicted across both contexts, most of them (1,163) of them were uniquely predicted in only one of the two (Figure 5) and were thus expected to affect KRAS signaling in context-specific fashion. For example: 1) CABYR (Figure 5C, magenta dot), the calcium-binding tyrosine phosphorylation-regulated protein, is overexpressed in lung cancer tumor samples and lung cancer cell-lines 97 , and its knockdown increases sensitivity to drug-induced apoptosis 98 . It is transcriptionally repressed in colon cancer cell lines, and knockdown of its repressor increases its expression 99 , elevates apoptosis, and suppresses proliferation 100 .…”

Section: Discussionmentioning

confidence: 99%

Systematic Elucidation and Validation of OncoProtein-Centric Molecular Interaction Maps

Broyde

Simpson

Murray

et al. 2018

Preprint

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“…In our previous study, we verified CABYR as a novel cancer testis antigen in lung cancer [ 2 ]. In addition to lung cancer and brain tumors [ 2 – 3 ], CABYR was also shown to be aberrantly expressed in liver cancer and esophageal cancer [ 4 ]. Knockdown of CABYR-c in HepG2 cells resulted in the inhibition of cell growth [ 5 ].…”

Section: Introductionmentioning

confidence: 99%

“…Knockdown of CABYR-c in HepG2 cells resulted in the inhibition of cell growth [ 5 ]. However, few studies have evaluated the biological functions of CABYR in cancer cells, with the exception of studies performed in liver and lung cancer cells [ 4 , 6 ]. Therefore, the full biological functions of CABYR in cancer cells have yet to be elucidated.…”

Section: Introductionmentioning

confidence: 99%

Depletion of CABYR-a/b sensitizes lung cancer cells to TRAIL-induced apoptosis through YAP/p73-mediated DR5 upregulation

et al. 2016

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Expression of the sperm fibrous sheath protein CABYR in human cancers and identification of α-enolase as an interacting partner of CABYR-a

Cited by 8 publications

References 24 publications

Gene-metabolite profile integration to understand the cause of spaceflight induced immunodeficiency

Gene-metabolite profile integration to understand the cause of spaceflight induced immunodeficiency

Systematic Elucidation and Validation of OncoProtein-Centric Molecular Interaction Maps

Depletion of CABYR-a/b sensitizes lung cancer cells to TRAIL-induced apoptosis through YAP/p73-mediated DR5 upregulation

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