Potential Significance of EMP3 in Patients with Upper Urinary Tract Urothelial Carcinoma: Crosstalk with ErbB2-PI3K-Akt Pathway

Wang, Yi Wen; Li, Wei Ming; Wu, Wen‐Jeng; Chai, Chee‐Yin; Liu, Hsiao Sheng; Lai, Ming Derg; Chow, Nan Haw

doi:10.1016/j.juro.2013.12.001

Cited by 32 publications

(43 citation statements)

References 28 publications

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“…EMP3 was reported to potentially have an influence on signal transduction and cell proliferation in different cancer cell lines by several studies and the results of our interaction screening further support this hypothesis. To verify if EMP3 has an influence on signal transduction and cell viability we generated cell lines with a stable knockdown of EMP3.…”

Section: Resultssupporting

confidence: 83%

“…In primary breast carcinoma, elevated EMP3 expression correlated with higher tumor grade, lymph node metastasis and strong expression of HER2 . In urothelial carcinoma, overexpression of EMP3 was significantly associated with poor patient progression‐free and metastasis‐free survival and was also linked to upregulation of HER2 and activation of the HER2‐PI3K‐AKT pathway . In hepatocellular carcinoma, strong expression of EMP3 was significantly correlated to expression of PI3K p85 regulatory subunit, phospho‐AKT, uPA and MMP‐9 and to poor state of differentiation .…”

Section: Introductionmentioning

confidence: 94%

“…In a study by Wilson et al ., it was shown that EMP3 interacts with the purinergic P2X7 receptor and overexpression of EMP3 led to membrane blebbing and initiation of apoptosis in HEK293 cells . In contrast, in urothelial carcinoma cells, ectopic overexpression of EMP3 was associated with enhanced proliferation, migration and activation of the HER2‐PI3K‐Akt signaling pathway . Several studies have demonstrated that knockdown of EMP3 inhibited tumorigenic parameters like proliferation, colony formation and/or invasion in different cancer cell lines.…”

Section: Introductionmentioning

confidence: 99%

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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: Resultssupporting

confidence: 83%

Section: Introductionmentioning

confidence: 94%

Section: Introductionmentioning

confidence: 99%

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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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“…In vitro studies validated the upregulation of ErbB2 in human UC cells and linked activation of ErbB2-PI3K-AKT pathway to increased expression of EMP3. 101 These findings suggest EMP3 possess cell proliferative properties in UUT-UC. Further research is needed to validate the potential of EMP3-mediated ErbB2 targeted therapy in UUT-UC.…”

Section: Emps (Emp1 Emp2 and Emp3)mentioning

confidence: 83%

Review of the GAS3 Family of Proteins and their Relevance to Cancer

Ashki¹,

Gordon

Wadehra

2015

Crit Rev Oncog

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The GAS3 family of tetraspan proteins has recently been implicated in the progression of cancer. Currently, six members of the GAS3 family have been identified in humans and mice, and while their expressions in disease vary, data suggest that they play a role in epithelial cell structure and function. In this review, we highlight the studies implicating four of the members in disease pathogenesis as well as probe the structural similarities between the family members. Finally, the impact of targeting select members of the family such as PMP22 and EMP2 is discussed.

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“…Numerous studies investigated the prognostic impact of various tissue-based molecular markers that are related to cellular processes such as cell adhesion (Metalloproteinase-9, E-cadherin [33], ParvB [34], snail [35], b-catenin[36]), cell signaling (EGFR[37], EMP3 [38], HER2 [4], PI3K/AKT [39, 40], IGFBP-5 [41], mTOR [42]), angiogenesis (Hypoxia-inducible factor-1[43]), cell proliferation (Ki67[44], p27 [45],cyclin D[46], NF- κ B [47], Aurora-A[48]), cell transport (GRP78 [49]) and apoptosis (bcl-2, survivin [50]). Recently, Wu et al compared the genome-wide mRNA expression profile using digital gene expression sequencing of tumors and matched normal tissues in 10 UTUC patients.…”

Section: Potential Biomarkers From Gene Expression Profilingmentioning

confidence: 99%

Prognostic Genetic Signatures in Upper Tract Urothelial Carcinoma

Bagrodia

Eugene

2016

Curr Urol Rep

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Urothelial carcinoma is a highly heterogeneous disease that can arise throughout the entire urothelial lining from the renal pelvis to the proximal urethra. Upper tract urothelial carcinoma (UTUC) is rare and while it shares many similarities with urothelial carcinoma of bladder (UCB), there are also significant differences between UTUC and UCB regarding clinical management and outcomes. No major advances have been made recently in the development of new systemic therapies for urothelial carcinoma, partly due to the lack of understanding of underlying molecular pathogenetic mechanisms. In the past decade, the emergence of next-generation sequencing has greatly enabled genomic characterization of tumor samples. Researchers are currently exploring a personalized approach to augment traditional clinical decision-making based on genetic alterations. In the present review, we summarize current genomic advances in UTUC and discuss the potential implications of these developments for developing prognostic and predictive biomarkers.

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Potential Significance of EMP3 in Patients with Upper Urinary Tract Urothelial Carcinoma: Crosstalk with ErbB2-PI3K-Akt Pathway

Abstract: EMP3 is an important prognostic indicator for selecting patients with upper urinary tract urothelial carcinoma for more intensive therapy. EMP3 is an innovative co-targeting candidate for designing ErbB2 based cancer therapy.

Cited by 32 publications

References 28 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

Review of the GAS3 Family of Proteins and their Relevance to Cancer

Prognostic Genetic Signatures in Upper Tract Urothelial Carcinoma

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