TNFα driven HIF-1α-hexokinase II axis regulates MHC-I cluster stability through actin cytoskeleton

Ghosh, Sadashib; Gupta, Piyushi; Sen, Ellora

doi:10.1016/j.yexcr.2015.11.016

Cited by 12 publications

(7 citation statements)

References 44 publications

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“…6i-k), highlighting HIF-1α as a critical effector of PTBP3-mediated malignant features. VEGFA, LDHA, HK2 and PLOD2 are the known target genes regulated by HIF-1α [21, 28–30]. Herein, we analyzed the correlation between PTBP3 mRNA level and HIF-1α target genes in public dataset (GEO: GSE40967), results showed that PTBP3 was positively correlated with VEGFA, LDHA, HK2 and PLOD2 (Fig.…”

Section: Resultsmentioning

confidence: 99%

PTBP3 contributes to colorectal cancer growth and metastasis via translational activation of HIF-1α

Hou

Chen

Yong

et al. 2019

J Exp Clin Cancer Res

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Background Colorectal cancer (CRC) remains the fourth most common cause of cancer-related mortality worldwide. We aimed to identify key molecules and signalling pathways mediating CRC growth and metastasis. Polypyrimidine tract-binding protein 3 (PTBP3) is a member of PTB family. A prooncogenic role for PTBP3 has also been discovered in several kinds of tumors. However, the expression and biological functions of the PTBP3 are still unknown in CRC. Methods We analysed the expression levels of PTBP3 using tissue microarray containing 568 CRC tissues and corresponding non-tumor adjacent tissues. The correlations between the PTBP3 expression level and clinicopathological features were evaluated using the chi-square test. The functional characterization for the role and molecular mechanism of PTBP3 in CRC was investigated through a series of in vitro and in vivo experiments. Results We showed that PTBP3 expression was increased in human CRC, and high PTBP3 expression was correlated with poor five-year overall survival and disease-free survival. Moreover, PTBP3 promoted tumor cell proliferation, migration and invasion in vitro and tumor growth and metastasis in vivo. PTBP3 enhanced HIF-1α protein expression by directly binding to the 5′UTR HIF-1α mRNA and activated translation of HIF-1α. Furthermore, HIF-1α was responsible for PTBP3-induced cell migration and invasion. Conclusions PTBP3 appears to be a novel oncogene of CRC through binding to the IRES region of HIF-1α mRNA, which regulates HIF-1α translation. PTBP3 can serve as a promising predictive biomarker for recurrence and prognosis in patients with CRC. Electronic supplementary material The online version of this article (10.1186/s13046-019-1312-y) contains supplementary material, which is available to authorized users.

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Section: Resultsmentioning

confidence: 99%

PTBP3 contributes to colorectal cancer growth and metastasis via translational activation of HIF-1α

Hou

Chen

Yong

et al. 2019

J Exp Clin Cancer Res

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“…Ten other families were identified with pronounced exclusivity, with IC less than 0.8: the anion-exchange and basigin related proteins, the carbonic anhydrases, intercellular adhesion molecule, interleukin-1 receptor family, phospholipase C, the sodium/potassium transporting ATPase gamma subunit, the hexokinases and the non-muscle myosin heavy-chain. Most of them directly affect cell adhesion ( Figure 7 ), but even hexokinases can affect motor or cytoskeletal proteins, and thus regulate cellular adhesion ( Hsu et al, 2010 ; Ghosh et al, 2016 ). Ion transport is the second most overrepresented function in the detected families.…”

Section: Discussionmentioning

confidence: 99%

Gene Families With Stochastic Exclusive Gene Choice Underlie Cell Adhesion in Mammalian Cells

Iakovlev

Faravelli

Becskei

2021

Front. Cell Dev. Biol.

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Exclusive stochastic gene choice combines precision with diversity. This regulation enables most T-cells to express exactly one T-cell receptor isoform chosen from a large repertoire, and to react precisely against diverse antigens. Some cells express two receptor isoforms, revealing the stochastic nature of this process. A similar regulation of odorant receptors and protocadherins enable cells to recognize odors and confer individuality to cells in neuronal interaction networks, respectively. We explored whether genes in other families are expressed exclusively by analyzing single-cell RNA-seq data with a simple metric. This metric can detect exclusivity independently of the mean value and the monoallelic nature of gene expression. Chromosomal segments and gene families are more likely to express genes concurrently than exclusively, possibly due to the evolutionary and biophysical aspects of shared regulation. Nonetheless, gene families with exclusive gene choice were detected in multiple cell types, most of them are membrane proteins involved in ion transport and cell adhesion, suggesting the coordination of these two functions. Thus, stochastic exclusive expression extends beyond the prototypical families, permitting precision in gene choice to be combined with the diversity of intercellular interactions.

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“…Ten other families were identified with pronounced exclusivity, with IC less than 0.8: the anion-exchange and basigin related proteins, the carbonic anhydrases, intercellular adhesion molecule, interleukin-1 receptor family, phospholipase C, the sodium/potassium transporting ATPase gamma subunit, the hexokinases and the non-muscle myosin heavy-chain. Most of them are directly affect cell adhesion ( Figure 7), but even hexokinases can affect motor or cytoskeletal proteins, and thus regulate cellular adhesion (63,64). Ion transport is the second most overrepresented function in the detected families.…”

Section: Discussionmentioning

confidence: 99%

Gene families with stochastic exclusive gene choice underlie cell adhesion in mammalian cells

Iakovlev

Faravelli

Becskei

2020

Preprint

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Exclusive stochastic gene choice combines precision with diversity. This regulation enables most T-cells to express exactly one T-cell receptor isoform chosen from a large repertoire, and to react precisely against diverse antigens. Some cells express two receptor isoforms, revealing the stochastic nature of this process. A similar regulation of odorant receptors and protocadherins enable cells to recognize odors and confer individuality to cells in neuronal interaction networks, respectively. We explored whether genes in other families are expressed exclusively by analyzing single cell RNA-seq data with a simple metric. Chromosomal segments and families are more likely to express genes concurrently than exclusively, possibly due to the evolutionary and biophysical aspects of shared regulation. Nonetheless, gene families with exclusive gene choice were detected in multiple cell types, most of them are membrane proteins involved in ion transport and cell adhesion, suggesting the coordination of these two functions. Thus, stochastic exclusive expression extends beyond the prototypical families, permitting precision in gene choice to be combined with the diversity of intercellular interactions.

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TNFα driven HIF-1α-hexokinase II axis regulates MHC-I cluster stability through actin cytoskeleton

Cited by 12 publications

References 44 publications

PTBP3 contributes to colorectal cancer growth and metastasis via translational activation of HIF-1α

PTBP3 contributes to colorectal cancer growth and metastasis via translational activation of HIF-1α

Gene Families With Stochastic Exclusive Gene Choice Underlie Cell Adhesion in Mammalian Cells

Gene families with stochastic exclusive gene choice underlie cell adhesion in mammalian cells

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