張純純 教授

學群：農業及海洋生物科技產業學群

研究專長：發育生物學、細胞生物學、內分泌學

E-mail：ccjang@mail.ncku.edu.tw

研究室：89807

研究室Tel：+886-6-2757575#58220

實驗室Tel：+886-6-2757575#58224#811

細胞遷移在生物學是一複雜且重要的研究課題，此一步驟影響層面極廣，包含胚胎發育時各胚層的遷移，發炎反應時免疫細胞如何迅速到達目的地以殺死入侵病源，個体受傷時的傷口癒合，甚至癌細胞的轉移, 這些都是我們有興趣的研究方向。本實驗室主要利用在果蠅一群會遷移的上皮細胞 (Border cells)為生物模式，研究細胞遷移及癌症轉移的分子機轉。

	During development, elaborate patterns of cell differentiation and movement unfold in the correct locations and at the proper times as a result of programmed changes in patterns of gene expression. Precise spatial patterns of gene expression commonly develop in response to graded morphogens, which cause distinct patterns of gene expression at different concentrations and thereby pattern cell fates. To address this topic, we took advantage of a group of migratory cells called border cells (BCs), which are derived from the follicular epithelium and migrate collectively within the egg chamber during Drosophila oogenesis. Four to six motile cells are recruited by a pair of polar cells to form a cluster. And these extend protrusions that guide the cluster through the confined space between nurse cells to reach the oocyte.
	Collective migration is important to embryonic development and cancer metastasis, but migratory and nonmigratory cell fate discrimination by differential activity of signal pathways remains elusive. In Drosophila oogenesis, Jak/Stat signaling patterns the epithelial cell fates in early egg chambers but later renders motility to clustered border cells. How Jak/Stat signal spatiotemporally switches static epithelia to motile cells is largely unknown. We report that a nuclear protein, Dysfusion, resides on the inner nuclear membrane and interacts with importin α/β and Nup153 to modulate Jak/Stat signal by attenuating Stat nuclear import. Dysfusion is ubiquitously expressed in oogenesis but specifically down-regulated in border cells when migrating. Increase of nuclear Stat by Dysfusion down-regulation triggers invasive cell behavior and maintains persistent motility. Mammalian homolog of Dysfusion (NPAS4) also negatively regulates the nuclear accumulation of STAT3 and cancer cell migration. Thus, our finding demonstrates that Dysfusion-dependent gating mechanism is conserved and may serve as a therapeutic target for Stat-mediated cancer metastasis.