Hematopoietic pre‐B cell leukemia transcription factor interacting protein is overexpressed in gastric cancer and promotes gastric cancer cell proliferation, migration, and invasion

Feng, Yingying; Li, Ling; Zhang, Xiaomei; Zhang, Yunjing; Liang, Yingchun; Lv, Jinjing; Zhang, Fan; Guo, Jing; Tian, Hong; Ji, Beibei; Ji, Quanbo; Guo-Hui, Mei; Ding, Lihua; Zhang, Shu; Xu, Xiaowei; Ye, Qinong

doi:10.1111/cas.12754

Cited by 26 publications

(24 citation statements)

References 35 publications

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“…HPIP has been reported to be overexpressed in many types of cancers, including colorectal cancer (15), astrocytoma (16), thyroid carcinoma (17), breast cancer (18), non-small cell lung cancer (19) and hepatocellular carcinoma (20), and plays an important role in the development and progression of these tumors. In GC, the expression of HPIP was found to be significantly upregulated in tumors compared with that noted in adjacent normal tissues and was found to be positively correlated with tumor size and metastasis (21). HPIP overexpression was found to increase GC cell proliferation by promoting cell cycle progression and to enhance GC cell migration by modulating epithelial-mesenchymal transition (EMT) (21).…”

Section: Introductionmentioning

confidence: 99%

HPIP promotes gastric cancer cell proliferation through activation of cap-dependent translation

et al. 2016

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Cap-dependent translation has an essential role in the control of cell proliferation by initiating the translation of oncogenes involved in the regulation of cell cycle progression, such as cyclin D1, and its deregulation contributes to the development and progression of various types of cancers. Hematopoietic pre-B-cell leukemia transcription factor interacting protein (HPIP) was found to be overexpressed in gastric cancer (GC) tissues compared to normal tissues and to promote GC growth in vitro and in vivo. However, the mechanism by which HPIP promotes GC cell proliferation remains unknown. In the present study, we found that HPIP activated cap-dependent translation in an AKT/mTORC1 pathway-dependent manner. Blocking cap‑dependent translation with 4EGI-1, a specific eIF4E/eIF4G interaction inhibitor, profoundly abrogated the ability of HPIP to promote G1/S phase transition and GC cell proliferation, while activation of cap-dependent translation by silencing 4E-BP1 expression significantly reversed the inhibitory effect of HPIP knockdown on GC cell proliferation. Furthermore, targeting translation initiation with 4EGI-1 effectively suppre-ssed the ability of HPIP to promote gastric tumor growth in a xenograft mouse model in vivo. All these data indicate that HPIP promotes GC cell proliferation through positive regulation of cap-dependent translation and mproves our understanding of the underlying mechanisms involved in the regulation of GC cell proliferation by HPIP.

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Section: Introductionmentioning

confidence: 99%

HPIP promotes gastric cancer cell proliferation through activation of cap-dependent translation

et al. 2016

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“…We also exemplified our hypothesized mechanism by an H3K36me3-associated isoforms switch of PBX1. In addition to its well-known functions in lymphoblastic leukemia (Kamps and Baltimore 1993;Foa et al 2000;Tesanovic et al 2014;Melendez et al 2015) and a number of cancers (Berge et al 2006;Qiu et al 2007;Park et al 2008;Magnani et al 2011;Thiaville et al 2012;Li et al 2014;Feng et al 2015;Jung et al 2015;Magnani et al 2015;Jung et al 2016), PBX1 was also found to promote hESC self-renewal by corporately binding to the regulatory elements of NANOG with KLF4 (Chan et al 2009). We found that the transcriptions of two isoforms of PBX1, PBX1a and PBX1b, are putatively regulated by H3K36me3 during hESC differentiation.…”

Section: Discussionmentioning

confidence: 99%

“…PBX1 was one of the genes that their ASs are positively associated with H3K36me3 ( Figures 5A, B). Its protein, PBX1, is a member of the TALE (three-amino acid loop extension) family homeodomain transcription factors (Chang et al 1997;Merabet and Mann 2016) and well known for its functions in lymphoblastic leukemia (Kamps and Baltimore 1993;Foa et al 2000;Tesanovic et al 2014;Melendez et al 2015) and several cancers (Berge et al 2006;Qiu et al 2007;Park et al 2008;Magnani et al 2011;Thiaville et al 2012;Li et al 2014;Feng et al 2015;Jung et al 2015;Magnani et al 2015;Jung et al 2016). PBX1 also plays roles in regulating developmental gene expression (Kim et al 2002) and maintaining stemness and self-renewal (Ficara et al 2008;Jung et al 2016), and in cell-cycle progression by repressing the cell-cycle inhibitor CDKN2B to promote transition to S phase (Koss et al 2012).…”

Section: H3k36me3-associated Isoform Switch Of Pbx1 Contributes To Hementioning

confidence: 99%

Alternative splicing links histone modifications to stem cell fate decision

Zhao

Olson

et al. 2017

Preprint

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Understanding embryonic stem cell (ESC) fate decision between self-renewal and proper differentiation is important for developmental biology and regenerative medicine. Attentions have focused on underlying mechanisms involving histone modifications (HMs), alternative pre-mRNA splicing (AS), and cell-cycle progression. However, their intricate interrelations and joint contributions to ESC fate decision remain unclear. We performed integrative analyses on transcriptomic and epigenomic data derived from human ESC (hESC) and five types of differentiated cells. We identified thousands of AS exons and revealed their development-and lineage-dependent characterizations. Following the observation that dynamic HM changes predominantly occur in AS exons upon hESCs differentiation, we identified 3 of 16 investigated HMs (H3K36me3, H3K27ac, and H4K8ac) that are strongly associated with 52.8% of hESC differentiation-related AS events. Further analyses showed that the HM-associated AS genes predominantly function in G2/M phases and ATM/ATR-mediated DNA damage response pathway for cell differentiation, whereas HM-unassociated AS genes enrich in G1 phase and pathways for self-renewal. These results imply a potential epigenetic mechanism by which some HMs contribute to ESC fate decision through the AS regulation of specific pathways and cell-cycle genes. We exemplified the potential mechanism by a cell cycle-related transcription factor, PBX1, which regulates the pluripotency regulatory network by binding to NANOG. We found that the isoform switch between PBX1a and PBX1b is strongly associated with H3K36me3 alteration and implicated in hESC fate determination. Supported by extended dataset from Roadmap/ENCODE projects, we identified the alternative splicing of PBX1 as a novel candidate linking H3K36me3 to embryonic stem cell fate decision.

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“…High expression of HPIP leads to activation of some oncogenes, such as cyclin A, cyclin B, and cyclin D1 in some cell lines 7. Recent studies also demonstrated a key role of HPIP in signal transduction pathways, thereby promoting cell proliferation.…”

Section: Discussionmentioning

confidence: 99%

“…Hematopoietic pre-B cell leukemia transcription factor (PBX)-interacting protein (HPIP) is a novel oncogene that is overexpressed in various human cancers, such as non-small-cell lung cancer,4 human spinal glioblastoma,5 thyroid cancer,6 gastric cancer,7 colorectal cancer,8 breast infiltrative ductal carcinoma,9 oral carcinogenesis,10 liver cancer,11 and human melanoma cell 12. Recent studies have demonstrated the multifaceted role of HPIP in pathways associated with cancer progression, including transformation, apoptosis, invasion, and metastasis 4,6,13,14.…”

Section: Introductionmentioning

confidence: 99%

Expression of HPIP in epithelial ovarian carcinoma: a clinicopathological study

Wang

Meng

Liu

et al. 2016

OTT

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ObjectivesHematopoietic pre-B-cell leukemia transcription factor (PBX)-interacting protein (HPIP) plays an important role in cancer invasion and metastasis. The aim of this study is to investigate the expression of HPIP in epithelial ovarian cancer (EOC).Patients and methodsImmunohistochemical method was performed using 42 normal ovarian specimens and 145 specimens with EOC. The correlations of HPIP expression with the clinicopathological factors and prognosis of EOC patients were evaluated. Statistical analyses were performed using the chi-square test, multivariate Cox proportional hazard, and Kaplan–Meier method.ResultsHPIP expression in EOC was higher than that in normal tissues (P<0.001). HPIP expression was significantly associated with histological grade, International Federation of Gynecology and Obstetrics stage, and lymphatic metastasis of EOC (P<0.05). Patients with high HPIP expression had poorer overall survival and disease-free survival (P<0.001) compared with patients with low HPIP expression. Multivariate Cox analysis demonstrated that HPIP was an independent factor for overall survival and disease-free survival (P<0.05).ConclusionHPIP may be a valuable biomarker for predicting the prognosis of EOC patients and may serve as a potential target for cancer therapy.

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Hematopoietic pre‐B cell leukemia transcription factor interacting protein is overexpressed in gastric cancer and promotes gastric cancer cell proliferation, migration, and invasion

Cited by 26 publications

References 35 publications

HPIP promotes gastric cancer cell proliferation through activation of cap-dependent translation

HPIP promotes gastric cancer cell proliferation through activation of cap-dependent translation

Alternative splicing links histone modifications to stem cell fate decision

Expression of HPIP in epithelial ovarian carcinoma: a clinicopathological study

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