Signal Transduction in the Erythropoietin Receptor System

Wojchowski, Don M.; Gregory, Richard C.; Miller, Chris P.; Pandit, Ajay K.; Pircher, Tony J.

doi:10.1006/excr.1999.4673

Cited by 203 publications

(83 citation statements)

References 224 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Ligand engagement of EPOR results in the activation of multiple signal transduction cascades including the JAK-STAT pathway (Wojchowski et al, 1999). To assess the possible role of JAK-STAT signaling in EPOmediated invasion by HNSCC cells, we employed the JAK inhibitor, AG490 (Meydan et al, 1996).…”

Section: Jak Inhibitor (Ag490) Blocks Hnscc Cell Invasionmentioning

confidence: 99%

“…Homodimerization of EPOR subunits stimulates numerous signaling pathways including activation of Lyn kinase, phosphatidylinositol 3-kinase and phospholipase C-g (Wojchowski et al, 1999). The Janus kinase 2 (JAK2) is also recruited to the receptor complex and activates the signal transducer and activator of transcription (STAT) factors, STAT-5A and STAT-5B (Ihle et al, 1995;Liu et al, 1998).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Erythropoietin-mediated activation of JAK-STAT signaling contributes to cellular invasion in head and neck squamous cell carcinoma

et al. 2005

View full text Add to dashboard Cite

Originally characterized as a growth factor for erythrocytes, erythropoietin (EPO) is used to treat anemia and fatigue in cancer patients receiving radiation therapy and chemotherapy. EPO and the EPO receptor (EPOR) are expressed in nonhematopoietic cells and cancers. However, the role of EPO and EPOR within nonhematopoietic cancer cells remains incompletely understood. Although a recent clinical trial demonstrated worse tumor control and survival in head and neck cancer patients treated with EPO, the role of EPO and EPOR in head and neck squamous cell carcinoma (HNSCC) has not been examined. In the present study, we demonstrate the previously unrecognized EPO-mediated invasion by HNSCC cells through the Janus kinase (JAK)-signal transducer and activator of transcription (STAT) signaling pathway. Furthermore, we confirmed the expression of EPO and EPOR in a panel of human HNSCC cell lines and tissue specimens. Pharmacological doses of EPO also had a limited proliferation effect in these cell lines. These results define a novel role for EPO in mediating tumor cell invasion. Increased levels of EPO and EPOR in lymph node metastases as compared to primary tumors from HNSCC patients further support the role of EPO/EPOR in HNSCC disease progression and metastasis.

show abstract

Section: Jak Inhibitor (Ag490) Blocks Hnscc Cell Invasionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Erythropoietin-mediated activation of JAK-STAT signaling contributes to cellular invasion in head and neck squamous cell carcinoma

et al. 2005

View full text Add to dashboard Cite

show abstract

“…Epo stimulation of erythroid cells also leads to the activation of the STAT5 transcription factors (for reviews see Wojchowski et al, 1999;Co er et al, 2000;Smithgall et al, 2000). Besides the well-known STAT dimers, heterodimers of STAT5 and CRKL were reported upon Epo-treatment of cells in several studies, and also with other cell stimuli Ota et al, 1998;Ozaki et al, 1998;and others).…”

Section: Stat5mentioning

confidence: 99%

“…In erythroid cells stimulated with Epo, Gab1 and Gab2 are also heavily tyrosinephosphorylated (Wickrema et al, 1999) and recruited to the Epo receptor-connected signalling complex. CRKL is also recruited into this complex (reviewed in Wojchowski et al, 1999). The situation is therefore reminiscent of c-Cbl, which also binds to Crk when it is tyrosine phosphorylated after Epo-stimulation of cells Chin et al, 1997).…”

Section: Gab Proteinsmentioning

confidence: 99%

Crk family adaptors–signalling complex formation and biological roles

2001

View full text Add to dashboard Cite

“…Erythropoietin (Epo) 1 is a hematopoietic growth factor that regulates proliferation, differentiation, and viability of erythroid progenitors and precursors (1)(2)(3). Regulation of intracellular calcium ([Ca] i ) by erythropoietin is one of the signaling mechanisms controlling proliferation and differentiation of erythroid cells (4 -10).…”

mentioning

confidence: 99%