EMP1, EMP 2, and EMP3 as novel therapeutic targets in human cancer

Wang, Yi Wen; Cheng, Hong; Ding, Ya; Chou, Lien Hsuan; Chow, Nan Haw

doi:10.1016/j.bbcan.2017.04.004

Cited by 66 publications

(60 citation statements)

References 135 publications

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“…The results indicate that EMP3 is required for maintaining elevated levels of mitogenic signaling as well as cell survivability in our cell line model. This is in line with other studies that have associated EMP3 with the regulation of cell proliferation, apoptosis and cellular signaling pathways . Of particular interest is EMP3’s role in cancer development and progression.…”

Section: Discussionsupporting

confidence: 90%

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Characterization of the epithelial membrane protein 3 interaction network reveals a potential functional link to mitogenic signal transduction regulation

Christians

Poisel

Hartmann

et al. 2019

Intl Journal of Cancer

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Epithelial Membrane Protein 3 (EMP3), a 4‐transmembrane glycoprotein, first gained attention as a putative tumor suppressor. Accumulating evidence, however, points to a more tumor promotive function of EMP3. The biological function of EMP3 remains largely unclear. To elucidate more of EMP3’s interaction network, we performed a Yeast‐Two‐Hybrid (Y2H) screening, followed by validation of candidate interactors by Biomolecular Fluorescence Complementation (BiFC) and Proximity Ligation Assay (PLA). Furthermore, we generated stable EMP3 knockdown cell lines and measured cell proliferation, migration and sensitivity to apoptosis induction as well as the expression and activation levels of important signal pathway components. The Y2H screening yielded 10 novel interactions of EMP3, eight of which could also be detected by BiFC and PLA interaction assays. All newly discovered interaction partners are involved in signaling or trafficking regulation. Most notably, FLOT1 and HTATIP2 have well described roles in the regulation of EGFR signaling. In addition, knockdown of EMP3 resulted in reduced levels of p‐AKT, p‐ERK and p‐EGFR, attenuated cell proliferation and migration and sensitized cells to apoptosis induction by TRAIL and Staurosporine. Based on these observations we hypothesize that EMP3 might be involved in the regulation of receptor‐tyrosine‐kinase mediated mitogenic signaling.

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Section: Discussionsupporting

confidence: 90%

“…In summary, EMP3 was reported to influence signaling by receptors like TGFBR2 and HER2 and it interacts with several proteins involved in differential spatial control or transduction mechanisms of mitogenic receptor signaling. This suggests that EMP3 plays an important role in organizing signaling complexes at the membrane.…”

Section: Discussionmentioning

confidence: 98%

Characterization of the epithelial membrane protein 3 interaction network reveals a potential functional link to mitogenic signal transduction regulation

Christians

Poisel

Hartmann

et al. 2019

Intl Journal of Cancer

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“…10 The EMP1 protein consists of 157 amino acids and is a glycoprotein containing four highly conserved hydrophobic transmembrane domains localized on the membrane. 11 Studies have shown that EMP1 plays a crucial part in cell adhesion, proliferation, apoptosis, differentiation, tumor formation and metastasis. 12,13 Li et al found that in glioblastoma, highly expressed EMP1 promotes tumor cell proliferation, invasion and metastasis by activating PI3K/AKT/mTOR signaling pathway.…”

Section: Introductionmentioning

confidence: 99%

<p>EMP1 Promotes the Proliferation and Invasion of Ovarian Cancer Cells Through Activating the MAPK Pathway</p>

Liu¹,

Ding²,

Nie³

et al. 2020

OTT

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Introduction: Epithelial membrane protein 1 (EMP1), a member of the EMP family, is overexpressed in a large number of tumors and is thought to be a cellular connexin on the cell membrane and is involved in proliferation, invasion, metastasis of tumor cells, and epithelial-mesenchymal transition (EMT). Nevertheless, its biomedical function in ovarian cancer is still unclear. Methods: EMP1 was detected in ovarian cancer cell lines by whole transcriptome resequencing. The mRNA of EMP1 was examined by qRT-PCR. The relationship between expression of EMP1 and clinical classification, metastasis, and shortened survival time in ovarian cancer specimens was analysed by immunohistochemical (IHC). The mechanism of EMP1 enhanced proliferation and invasion of ovarian cancer cells was determined by siRNA interference, colony formation, migration and invasion experiments, and Western blot. Results: EMP1 was up-regulated in ovarian cancer cell lines and ovarian cancer tissues in comparison with non-cancerous ovarian specimens. High expression of EMP1 in ovarian cancer specimens was obviously related to high clinical classification, metastasis, and shortened survival time. High expressed EMP1 facilitates cell proliferation, invasion and EMT in ovarian cancer cells. Over-expressed EMP1 increased the protein levels of RAS/ RAF/MAPK/c-JUN. Conclusion: Over-expressed EMP1 in ovarian cancer promotes tumor cell proliferation, invasion, and EMT by the MAPK signaling pathway.

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“…It is known that tumorigenesis is a complex process with abundant deregulated genes [6]. MicroRNAs (miRNAs) are considered a group of important molecules during tumorigenesis [7].…”

Section: Introductionmentioning

confidence: 99%

MicroRNA-1298 is downregulated in non-small cell lung cancer and suppresses tumor progression in tumor cells

Wang

et al. 2019

Diagn Pathol

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Background: MicroRNAs (miRNAs) have been reported to serve pivotal roles in tumorigenesis. This study sough to assess the expression and clinical significance of microRNA-1298 (miR-1298) in patients with non-small cell lung cancer (NSCLC), and explore the functional role of miR-1298 in tumorigenesis. Methods: One hundred and twenty-one NSCLC patients were recruited in this study. The expression of miR-1298 was estimated using quantitative real-time PCR. Kaplan-Meier survival curves and Cox regression analysis were used to evaluate the prognostic value of miR-1298. Gain-and loss-of-function experiments were preformed to explore the biological function of miR-1298 in NSCLC cells. Results: Expression levels of miR-1298 were downregulated in NSCLC tissues and cells compared with the corresponding normal controls. The decreased expression of miR-1298 was associated with patients' lymph node metastasis and TNM stage. The low expression of miR-1298 predicted poor overall survival and served as an independent prognostic indicator in NSCLC patients. According to the cell experiments, NSCLC cell proliferation, migration and invasion were inhibited by the overexpression of miR-1298. Conclusion: All the data indicated that the downregulation of miR-1298 predicts poor prognosis of NSCLC, and the overexpression of miR-1298 in NSCLC cells leads to inhibited tumorigenesis. The aberrant miR-1298 may serve as a novel biomarker and therapeutic target in NSCLC.

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EMP1, EMP 2, and EMP3 as novel therapeutic targets in human cancer

Cited by 66 publications

References 135 publications

Characterization of the epithelial membrane protein 3 interaction network reveals a potential functional link to mitogenic signal transduction regulation

Characterization of the epithelial membrane protein 3 interaction network reveals a potential functional link to mitogenic signal transduction regulation

<p>EMP1 Promotes the Proliferation and Invasion of Ovarian Cancer Cells Through Activating the MAPK Pathway</p>

MicroRNA-1298 is downregulated in non-small cell lung cancer and suppresses tumor progression in tumor cells

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