CHP2 Promotes Cell Proliferation in Breast Cancer via Suppression of FOXO3a

Zhao, Xiaohui; Xie, Tian; Dai, Ting; Zhao, Wenhui; Li, Jing; Xu, Rui; Jiang, Chao; Li, Peiqiong; Deng, Junyao; Su, Xiaobo; Ma, Ning‐Fang

doi:10.1158/1541-7786.mcr-18-0157

Cited by 12 publications

(13 citation statements)

References 46 publications

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“…calcineurin homologous protein isoform 2 (CHP2) is expressed in normal intestinal epithelia and also epithelium-like cell line [25], and it might act as a potential role in transmembrane Nat/Ht exchange which can protect cells from serum deprivation induced death [25,26]. The expression of CHP2 has been reported to be significantly increased in human ovarian carcinoma cells [27] and leukemia primary cells [28] and breast cancer cells [29]. Mechanistically, overexpression of CHP2 activated AKT signaling and suppressed the transactivation of the forkhead box O3 (FOXO3/FOXO3a) transcription factor in breast cancer [29].…”

Section: Discussionmentioning

confidence: 99%

“…The expression of CHP2 has been reported to be significantly increased in human ovarian carcinoma cells [27] and leukemia primary cells [28] and breast cancer cells [29]. Mechanistically, overexpression of CHP2 activated AKT signaling and suppressed the transactivation of the forkhead box O3 (FOXO3/FOXO3a) transcription factor in breast cancer [29]. Besides, a study conducted 10-gene signature including CHP2 found that high expression of CHP2 was associated with the recurrence of COAD [30].…”

Section: Discussionmentioning

confidence: 99%

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Identification of novel biomarkers affecting the metastasis of colorectal cancer through bioinformatics analysis and validation through qRT-PCR

et al. 2020

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Background: Tumor progression and distant metastasis are the main causes of deaths in colorectal cancer (CRC) patients, and the molecular mechanisms in CRC metastasis have not been completely discovered. Methods: We identified differentially expressed genes (DEGs) and lncRNAs (DELs) of CRC from The Cancer Genome Atlas (TCGA) database. Then we conducted the weighted gene co-expression network analysis (WGCNA) to investigate co-expression modules related with CRC metastasis. Gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, DEG-DEL co-expression network and survival analyses of significant modules were also conducted. Finally, the expressions of selected biomarkers were validated in cell lines by quantitative real-time PCR (qRT-PCR). Results: 2032 DEGs and 487 DELs were involved the construction of WGCNA network, and greenyellow, turquoise and brown module were identified to have more significant correlation with CRC metastasis. GO and KEGG pathway analysis of these three modules have proven that the functions of DEGs were closely involved in many important processes in cancer pathogenesis. Through the DEG-DEL co-expression network, 12 DEGs and 2 DELs were considered as hub nodes. Besides, survival analysis showed that 30 DEGs were associated with the overall survival of CRC. Then 10 candidate biomarkers were chosen for validation and the expression of CA2, CHP2, SULT1B1, MOGAT2 and C1orf115 were significantly decreased in CRC cell lines when compared to normal human colonic epithelial cells, which were consistent with the results of differential expression analysis. Especially, low expression of SULT1B1, MOGAT2 and C1orf115 were closely correlated with poorer survival of CRC. Conclusion: This study identified 5 genes as new biomarkers affecting the metastasis of CRC. Besides, SULT1B1, MOGAT2 and C1orf115 might be implicated in the prognosis of CRC patients.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Identification of novel biomarkers affecting the metastasis of colorectal cancer through bioinformatics analysis and validation through qRT-PCR

et al. 2020

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“…Previously, immunoblotting and RT-PCR techniques have demonstrated that NHE1 and CHP1 are ubiquitously expressed in human tissues while CHP2 is primarily expressed in the intestinal epithelium and in diseased cells including hepatoma, colon AC, cervical carcinoma, and acute leukemia as well as in breast, ovarian carcinoma, and lung cancer. 17,23,24,29 These methods have sampled CHP2 specifically in a limited subset of tissues and cancer types. To comprehensively understand the expression profiles of NHE1, CHP1, and CHP2 expression in non-diseased normal tissues, we analyzed archived RNA-Seq data from the Expression Atlas 31,32 (Figure 1(a)).…”

Section: Expression Profiles Of Nhe1 Chp1 and Chp2 In Normal Tissuesmentioning

confidence: 99%

“…This function likely acts via NHE1-CHP2 interaction to maintain pH i and may involve other signaling pathways like AKT/PKB to control cell proliferation and cell cycle. 29 Because this expression pattern is present in only a subset of cancers, it is likely a driver of tumorigenesis, but not necessary for cancer progression and may provide a general mechanism for increased tumorigenesis and metastasis across cancer types.…”

Section: Nhe1 Chp1 and Chp2 Expression In Lung Cancermentioning

confidence: 99%

Calcineurin homologous protein isoform 2 supports tumor survival via the sodium hydrogen exchanger isoform 1 in non-small cell lung cancer

et al. 2020

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Maintaining intracellular pH is crucial for preserving healthy cellular behavior and, when dysregulated, results in increased proliferation, migration, and invasion. The Na+/H+ exchanger isoform 1 is a highly regulated transmembrane antiporter that maintains pH homeostasis by exporting protons in response to intra- and extracellular signals. Activation of Na+/H+ exchanger isoform 1 is exquisitely regulated by the extracellular environment and protein cofactors, including calcineurin B homologous proteins 1 and 2. While Na+/H+ exchanger isoform 1 and calcineurin B homologous protein 1 are ubiquitously expressed, calcineurin B homologous protein 2 shows tissue-specific expression and upregulation in a variety of cancer cells. In addition, calcineurin B homologous protein 2 expression is modulated by tumorigenic extracellular conditions like low nutrients. To understand the role of calcineurin B homologous protein 2 in tumorigenesis and survival in lung cancer, we surveyed existing databases and formed a comprehensive report of Na+/H+ exchanger isoform 1, calcineurin B homologous protein 1, and calcineurin B homologous protein 2 expression in diseased and non-diseased tissues. We show that calcineurin B homologous protein 2 is upregulated during oncogenesis in many adeno and squamous carcinomas. To understand the functional role of calcineurin B homologous protein 2 upregulation, we evaluated the effect of Na+/H+ exchanger isoform 1 and calcineurin B homologous protein 2 depletion on cellular function during cancer progression in situ. Here, we show that calcineurin B homologous protein 2 functions through Na+/H+ exchanger isoform 1 to effect cell proliferation, cell migration, steady-state pH i, and anchorage-independent tumor growth. Finally, we present evidence that calcineurin B homologous protein 2 depletion in vivo has potential to reduce tumor burden in a xenograft model. Together, these data support the tumor-promoting potential of aberrant calcineurin B homologous protein 2 expression and position calcineurin B homologous protein 2 as a potential therapeutic target for the treatment of non-small cell lung cancer.

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“…Breast cancer is the most prevalent malignancies and the leading cause of cancer death among women . According to the statistics of the World Health Organization, about 2.1 million women suffer from breast cancer and an estimated 627 000 women died of breast cancer in 2018 .…”

Section: Introductionmentioning

confidence: 99%

Knockdown of XB130 restrains cancer stem cell‐like phenotype through inhibition of Wnt/β‐Catenin signaling in breast cancer

Xie

Jiang

Dai

et al. 2019

Molecular Carcinogenesis

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The cancer stem cells (CSCs) is a subset of cancer cells that possess stem cell properties, which plays a crucial role in the occurrence, metastasis, and recurrence of the tumor. XB130 is a novel adapter protein potentially serves as a functional factor in CSCs. To determine the role of CSCs in breast cancer, we focused on the study of XB130. In our study, we found that XB130 expression was signiﬁcantly upregulated in breast cancer and was closely related to the clinicopathologic characteristics, overall survival and poor prognosis of breast cancer patients. Functionally, we found that knockdown of XB130 was not only played an important role in proliferation, epithelial‐mesenchymal transition (EMT), and metastasis in breast cancer cells but also exhibited potent antitumor activity in animal tumor models. Moreover, we demonstrated that silencing endogenous XB130 regulated the cancer stem cell‐like properties of breast cancer, including the formation of self‐renewing spheres and the proportion of breast cancer SP+ cells. Mechanistically, our studies indicated that downregulation of XB130 restrained the EMT and Wnt/β‐catenin signaling, so as to weaken the tumor‐initiating cell‐like phenotype of breast cancer cells. This study indicates that XB130 plays an important role in maintaining the EMT and stem cell‐like characteristics of breast cancer cells, supporting the significance of XB130 as a new potential therapeutic target for early diagnosis and prognosis of breast cancer.

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CHP2 Promotes Cell Proliferation in Breast Cancer via Suppression of FOXO3a

Cited by 12 publications

References 46 publications

Identification of novel biomarkers affecting the metastasis of colorectal cancer through bioinformatics analysis and validation through qRT-PCR

Identification of novel biomarkers affecting the metastasis of colorectal cancer through bioinformatics analysis and validation through qRT-PCR

Calcineurin homologous protein isoform 2 supports tumor survival via the sodium hydrogen exchanger isoform 1 in non-small cell lung cancer

Knockdown of XB130 restrains cancer stem cell‐like phenotype through inhibition of Wnt/β‐Catenin signaling in breast cancer

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