Addiction of pancreatic cancer cells to zinc-finger transcription factor ZIC2

Oncotarget
Shingo InagumaKenji Kasai

Abstract

Activity of GLI transcription factors of Hedgehog signaling is key for various cancer cell properties, especially in pancreatic ductal adenocarcinoma (PDAC). Zinc-finger transcriptional regulators ZIC1 to ZIC5 of ZIC gene family were demonstrated to associate with GLI to increase the nuclear accumulation and transcriptional activity of GLI. Notwithstanding this supportive role for GLI-dependent transcription, it was not fully understood whether ZIC plays an independent role in cancer cell biology. Here, we found that ZIC2 is indispensable in the regulation of PDAC cell apoptosis. We found that human PDAC cell lines uniquely express ZIC2. ZIC2 knockdown induced PDAC cell apoptosis; conversely, ZIC2 over-expression enhanced the cellular proliferation. Through a comprehensive screening, we identified fibroblast growth factor receptor 3 (FGFR3) and ANNEXIN A8 (ANXA8) as genes up-regulated by ZIC2 in PDAC cells. The forced expression of these two genes cooperatively rescued the apoptosis of ZIC2-knockdown cells. Immunohistochemical analyses further supported the correlation of ZIC2 expression and these genes in human pancreata harboring PDAC. Intriguingly, the ZIC2-mediated up-regulation of FGFR3 and ANXA8 was indicated to be GLI -i...Continue Reading

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Citations

May 14, 2016·International Journal of Molecular Medicine·Gang MaQianjun Li
Nov 20, 2016·Pathology International·Kenji Kasai
Oct 16, 2019·Oncology Letters·Ting-Ting DingJi-Hong Feng
Sep 11, 2018·Oncotarget·Pushpinder Singh BawaSubhashini Srinivasan
Aug 23, 2020·Cancers·Stefano Rossetti, Nicoletta Sacchi
Oct 24, 2019·Clinical Epigenetics·Reka TothClarissa Gerhäuser
Jan 27, 2021·International Journal of Molecular Sciences·Sidney IrianaNeelam Sharma-Walia
Mar 6, 2021·Frontiers in Molecular Biosciences·Zhengtong LvYuan Li
Mar 31, 2021·Gynecologic Oncology·Neda RahimianHamed Mirzaei

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Methods Mentioned

BETA
electrophoretic mobility shift assay
transfection
cDNA array
nuclear translocation
immunoprecipitation
PCR
FACS
Assay

Software Mentioned

StatView
NIH Image

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