Abstract：
:It has been proposed that occult, disseminated metastatic cells are refractory to chemotherapy due to lack of proliferation. We have shown that p38 activation induces dormancy of squamous carcinoma cells. We now show that p38 signaling in these cells activates a prosurvival mechanism via the up-regulation of the endoplasmic reticulum (ER) chaperone BiP and increased activation of the ER stress-activated eukaryotic translation initiator factor 2alpha kinase RNA-dependent protein kinase-like ER kinase (PERK) allowing dormant tumor cells to resist drug toxicity. RNA interference and dominant-negative expression studies revealed that both BiP and PERK signaling promote survival and drug resistance of dormant cells, and that BiP up-regulation prevents Bax activation. We propose that stress-dependent activation of p38 via BiP up-regulation and PERK activation protects dormant tumor cells from stress insults, such as chemotherapy.
journal_name
Cancer Resjournal_title
Cancer researchauthors
Ranganathan AC,Zhang L,Adam AP,Aguirre-Ghiso JAdoi
10.1158/0008-5472.CAN-05-3092subject
Has Abstractpub_date
2006-02-01 00:00:00pages
1702-11issue
3eissn
0008-5472issn
1538-7445pii
66/3/1702journal_volume
66pub_type
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