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Autocrine/paracrine erythropoietin signalling promotes JAK/STAT‐dependent proliferation of human cervical cancer cells
Author(s) -
Lopez Tania V.,
Lappin Terence R.J.,
Maxwell Perry,
Shi Zhanzhong,
LopezMarure Rebeca,
Aguilar Cecilia,
RochaZavaleta Leticia
Publication year - 2011
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.25935
Subject(s) - erythropoietin receptor , erythropoietin , autocrine signalling , paracrine signalling , cancer research , cell growth , stat5 , erythropoiesis , cancer cell , biology , signal transduction , medicine , cancer , microbiology and biotechnology , receptor , endocrinology , anemia , genetics
Erythropoietin (Epo) regulates erythropoiesis by binding to its receptor (EpoR) and promoting cell proliferation, differentiation and inhibition of apoptosis. Epo is widely used to treat cervical cancer‐related anaemia. However, there are data suggesting that administration of Epo is associated with an increment in recurrence rate, and decreased disease‐free and overall survival. In the present study, we investigated the expression of Epo and EpoR on cervical cancer cell lines. We observed that both EpoR and extracellular Epo are constitutively expressed in cervical cancer cells. Inhibition of either Epo or EpoR expression with siRNA attenuated cell proliferation, whereas addition of exogenous Epo led to a significant increase in cell growth, both in vitro and in vivo . Epo‐induced proliferation was associated with the activation of JAK2, JAK3, STAT3 and STAT5 but not JAK1 and STAT1. Our results are consistent with the existence of a functional, endogenous Epo/EpoR system in cervical cancer with the capacity to activate the transduction of signals resulting in an increased proliferation potential.