Molecule Information

General Information of the Molecule (ID: Mol04397)

• Name: Epidermal growth factor receptor kinase substrate 8 (EPS8) ,Homo sapiens
• Molecule Type: Protein
• Gene Name: EPS8
• Gene ID: 2059
• Sequence:
  MNGHISNHPSSFGMYPSQMNGYGSSPTFSQTDREHGSKTSAKALYEQRKNYARDSVSSVS
  DISQYRVEHLTTFVLDRKDAMITVDDGIRKLKLLDAKGKVWTQDMILQVDDRAVSLIDL
  E SKNELENFPLNTIQHCQAVMHSCSYDSVLALVCKEPTQNKPDLHLFQCDEVKANLISE
  DI ESAISDSKGGKQKRRPDALRMISNADPSIPPPPRAPAPAPPGTVTQVDVRSRVAAWS
  AWA ADQGDFEKPRQYHEQEETPEMMAARIDRDVQILNHILDDIEFFITKLQKAAEAFSE
  LSKR KKNKKGKRKGPGEGVLTLRAKPPPPDEFLDCFQKFKHGFNLLAKLKSHIQNPSAA
  DLVHF LFTPLNMVVQATGGPELASSVLSPLLNKDTIDFLNYTVNGDERQLWMSLGGTWM
  KARAEW PKEQFIPPYVPRFRNGWEPPMLNFMGATMEQDLYQLAESVANVAEHQRKQEIK
  RLSTEHS SVSEYHPADGYAFSSNIYTRGSHLDQGEAAVAFKPTSNRHIDRNYEPLKTQP
  KKYAKSKY DFVARNNSELSVLKDDILEILDDRKQWWKVRNASGDSGFVPNNILDIVRPP
  ESGLGRADP PYTHTIQKQRMEYGPRPADTPPAPSPPPTPAPVPVPLPPSTPAPVPVSKV
  PANITRQNSS SSDSGGSIVRDSQRHKQLPVDRRKSQMEEVQDELIHRLTIGRSAAQKKF
  HVPRQNVPVIN ITYDSTPEDVKTWLQSKGFNPVTVNSLGVLNGAQLFSLNKDELRTVCP
  EGARVYSQITVQ KAALEDSSGSSELQEIMRRRQEKISAAASDSGVESFDEGSSH
• Function: Signaling adapter that controls various cellular protrusionsby regulating actin cytoskeleton dynamics and architecture. Dependingon its association with other signal transducers, can regulatedifferent processes. Together with SOS1 and ABI1, forms a trimericcomplex that participates in transduction of signals from Ras to Rac byactivating the Rac-specific guanine nucleotide exchange factor activity. Acts as a direct regulator of actin dynamics by binding actinfilaments and has both barbed-end actin filament capping and actinbundling activities depending on the context. Displays barbed-end actincapping activity when associated with ABI1, thereby regulating actin-based motility process: capping activity is auto-inhibited andinhibition is relieved upon ABI1 interaction. Also shows actin bundlingactivity when associated with BAIAP2, enhancing BAIAP2-dependentmembrane extensions and promoting filopodial protrusions. Involved inthe regulation of processes such as axonal filopodia growth,stereocilia length, dendritic cell migration and cancer cell migrationand invasion. Acts as a regulator of axonal filopodia formation inneurons: in the absence of neurotrophic factors, negatively regulatesaxonal filopodia formation via actin-capping activity. In contrast, itis phosphorylated in the presence of BDNF leading to inhibition of itsactin-capping activity and stimulation of filopodia formation.Component of a complex with WHRN and MYO15A that localizes atstereocilia tips and is required for elongation of the stereociliaactin core. Indirectly involved in cell cycle progression; itsdegradation following ubiquitination being required during G2 phase topromote cell shape changes. {ECO:0000269|PubMed:15558031,ECO:0000269|PubMed:17115031}.
• Uniprot ID: EPS8_HUMAN
• Ensembl ID: ENSG0000015149114
• HGNC ID: HGNC:3420

Kingdom: Metazoa
Phylum: Chordata
Class: Mammalia
Order: Primates
Family: Hominidae
Genus: Homo
Species: Homo sapiens

Type(s) of Resistant Mechanism of This Molecule

  UAPP: Unusual Activation of Pro-survival Pathway

Drug Resistance Data Categorized by Drug

Approved Drug(s) 1 drug(s) in total

Enzalutamide

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Prostate cancer [ICD-11: 2C82.0] [1]

• Resistant Disease: Prostate cancer [ICD-11: 2C82.0]
• Resistant Drug: Enzalutamide
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Ras/p53/JAK/PI3K signaling pathway; Regulation; N.A.
• In Vitro Model: LNCaP Enz-R cells; N.A.; Homo sapiens (Human); N.A.
• Experiment for Molecule Alteration: Western blot assay; qRT-PCR
• Experiment for Drug Resistance: CCK8 assay
• Mechanism Description: This study investigated the role of Eps8 in prostate cancer. The LNCaP cell line and enzalutamide-resistant LNCaP (LNCaP Enz-R) cell lines were utilized for the investigation. Overexpression of Eps8 was observed in the LNCaP Enz-R cells. Transfecting pCMV-EPS8 also increased the levels of epithelial-to-mesenchymal transition (EMT), cell proliferation, and cell viability in both cell lines. Conversely, knockdown of Eps8 expression decreased the levels of EMT, cell proliferation, and cell viability in both cell lines. Furthermore, EPS8-induced EMT activation could be reversed by suppressing the Ras/JAK/PI3K signaling pathway. In vivo animal study also confirmed the crucial role of Eps8 expression in prostate cancer progression.

References

• Ref 1: Knockdown of EPS8 expression attenuates the proliferation of enzalutamide-resistant prostate cancer cells. Am J Cancer Res. 2024 Oct 15;14(10):4717-4730.