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Eukaryotic Initiation Factor 2-associated glycoprotein P67 inhibits the tumorigenicity of Alveolar Rhabdomyosarcoma (ARMS) and involves its differentiation and migration

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2019, PHD, Kent State University, College of Arts and Sciences / Department of Chemistry and Biochemistry.
Rhabdomyosarcoma (RMS) is a soft tissue tumor that arises from connective tissue predominantly among children and adolescents. RMS may occur anywhere in the body with two main subtypes: Embryonal RMS (ERMS) and Alveolar RMS (ARMS), which are originally distinguished by different pathological morphologies by light microscope. ARMS is a high-grade malignant neoplasm and often time associated with a worse outcome than in patients with ERMS due to chromosomal translocation. Even though various approaches were developed, the five-year survival rate is still less than 50%. Rh30 cell line is widely appreciated to represent ARMS, because it renders significant characteristics of ARMS. In human cancers, such as ARMS, K-Ras is the frequently mutated isoform, leading to aberrant activation of ERK1/2 MAP Kinase pathway. We found out P67 functions as a tumor suppressor, which inhibits the tumorigenicity of Rh30 cells ex vivo and in vivo through inhibition of activation and activity of ERK1/2. In addition, P67 is involved in the differentiation of C2C12 myoblasts into multinucleated myotubes. Moreover, P67 is required for stable expression of focal adhesion kinase (FAK), a direct substrate of insulin and insulin like receptor tyrosine kinase receptor, as well involves differentiation of C2C12 cells into myotubes. In Rh30 cells, there is a strong association with dysregulation of insulin-like growth factor receptor, due to chromosomal translocation. Insulin-involved signaling pathway is implicated for myogenic differentiation of Rh30 cells. Therefore, insulin plays a pivotal role in the regulation of Rh30 cell differentiation. Given that, in this dissertation, we further validated P67 and insulin contribute to differentiation of incomplete differentiated Rh30 cells. The combinatory treatment of overexpression of P67 and insulin induced apoptosis and differentiation of Rh30 cells. Cell migration is a hallmark of complex biological processes during cell differentiation. P67 is involved in the regulation of Rho GTPase family, which are responsible for protrusive structures during migration. With these previous findings, we further investigated that overexpression of P67 can increase the migratory capacity of Rh30 cells via upregulation of specific small GTPases.
Bansihdar Datta, Ph.D. (Advisor)
115 p.

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Citations

  • Liu, H. (2019). Eukaryotic Initiation Factor 2-associated glycoprotein P67 inhibits the tumorigenicity of Alveolar Rhabdomyosarcoma (ARMS) and involves its differentiation and migration [Doctoral dissertation, Kent State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=kent1564585690280704

    APA Style (7th edition)

  • Liu, He. Eukaryotic Initiation Factor 2-associated glycoprotein P67 inhibits the tumorigenicity of Alveolar Rhabdomyosarcoma (ARMS) and involves its differentiation and migration. 2019. Kent State University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=kent1564585690280704.

    MLA Style (8th edition)

  • Liu, He. "Eukaryotic Initiation Factor 2-associated glycoprotein P67 inhibits the tumorigenicity of Alveolar Rhabdomyosarcoma (ARMS) and involves its differentiation and migration." Doctoral dissertation, Kent State University, 2019. http://rave.ohiolink.edu/etdc/view?acc_num=kent1564585690280704

    Chicago Manual of Style (17th edition)