GATA2-Mediated Transcriptional Activation of Notch3 Promotes Pancreatic Cancer Liver Metastasis

Heng Lin; Peng Hu; Hongyu Zhang; Yong Deng; Zhiqing Yang; Leida Zhang

doi:10.14348/molcells.2022.2176

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자료유형: 학술저널

저자정보: Heng Lin (Third Military Medical University (Army Medical University)) Peng Hu (Third Military Medical University (Army Medical University)) Hongyu Zhang (Third Military Medical University (Army Medical University)) Yong Deng (Third Military Medical University (Army Medical University)) Zhiqing Yang (Third Military Medical University (Army Medical University)) Leida Zhang (Third Military Medical University (Army Medical University))

저널정보: 한국분자세포생물학회 Molecules and Cells Molecules and Cells 제45권 제5호

발행연도: 2022.5

수록면: 329 - 342 (14page)

DOI: 10.14348/molcells.2022.2176

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The liver is the predominant metastatic site for pancreatic cancer. However, the factors that determine the liver metastasis and the specific molecular mechanisms are still unclear. In this study, we used human pancreatic cancer cell line Hs766T to establish Hs766T-L3, a subline of Hs766T with stable liver metastatic ability. We performed RNA sequencing of Hs766T-L3 and its parental cell line Hs766T, and revealed huge differences in gene expression patterns and pathway activation between these two cell lines. We correlated the difference in pathway activation with the expression of the four core transcriptional factors including STAT1, NR2F2, GATA2, and SMAD4. Using the TCGA database, we examined the relative expression of these transcription factors (TFs) in pan-cancer and their relationship with the prognosis of the pancreatic cancer. Among these TFs, we considered GATA2 is closely involved in tumor metastasis and may serve as a potential metastatic driver. Further in vitro and in vivo experiments confirmed that GATA2-mediated transcriptional activation of Notch3 promotes the liver metastasis of Hs766T-L3, and knockdown of either GATA2 or Notch3 reduces the metastatic ability of Hs766T-L3. Therefore, we claim that GATA2 may serve as a metastatic driver of pancreatic cancer and a potential therapeutic target to treat liver metastasis of pancreatic cancer.

#GATA2 #liver metastasis #Notch3 #RNA sequencing

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