研究發現高糖飲食 (High-Dietary Sugar, HDS) 會導致代謝失調，進而誘發
高血糖及糖尿病，而目前許多證據顯示糖尿病病患是特定癌症的高危險群。在
表觀遺傳學中，異染色質蛋白1 (Heterochromatin Protein 1, HP1) 主要除了調
控異染色質的形成，也參與抑制基因的表達。目前，在許多人類的癌症中發現
異染色質蛋白1 有表現量降低的現象。然而，高糖飲食所誘導的腫瘤進程是否
受到表關遺傳相關分子機制的調控目前並不清楚。所以本研究利用果蠅作為癌
症生物模式系統，探討異染色質是否及如何調控糖代謝和高糖飲食所誘導的腫
瘤進程。餵食帶有Ras/Src 誘導的腫瘤模式生物不同濃度的蔗糖，我們發現腫
瘤進程會隨著糖濃度的增加而加劇。並且，高糖飲食亦會導致異染色質的降低
及更惡化的腫瘤進程。另外，我們也發現異染色質的表現量對於抑制腫瘤生長、
影響癌症動物的發育與存活扮演重要的角色。在Ras/Src 誘導的腫瘤中過度表
達和降低異染色質蛋白1 表現可抑制腫瘤的生長，同時也改善動物的蛹化和羽
化率。在腫瘤動物中，全身性提高異染色質蛋白1 的表達可提升動物的蛹化和
羽化率；然而，全身性減少異染色質蛋白1 的表達則無法達到提升蛹化羽化率
的效果。有趣的是，在腫瘤進程中，我們觀察到成功羽化的母果蠅比例遠高於
公果蠅。此外，利用比對基因資料庫及測量mRNA 的表現量，我們找到數個受
到異染色質蛋白1 調控的代謝相關基因，顯示異染色質對於糖類代謝也很重要。
總結上述實驗，我們推測異染色質表現量的高低可能藉由調控代謝相關基因的
表達，進而抑制高糖導致的腫瘤生長。綜上所述，本研究有助於我們自表關遺
傳的角度，更進一步了解高糖誘導腫瘤進程的分子機制，並且為飲食所導致的
代謝疾病和相關癌症提供新的治療方向。

Increasing risks of specific cancers are found in patients with high dietary sugar
(HDS)-induced metabolic disorders, including hyperglycemia and diabetes mellitus.
Heterochromatin protein 1 (HP1) which forms heterochromatin and mediates
epigenetic gene silencing, is down-regulated in various human cancers. However,
underlying epigenetic mechanisms by which HDS leads to tumor progression are still
poorly understood. Here, we use Drosophila as a model to investigate whether and
how heterochromatin epigenetically regulates glucose metabolism and HDS-induced
tumor progression. By feeding Drosophila, which carry Ras/Src-transformed tumors,
with four different concentrations of sucrose from zero to 1.0M (HDS), we
demonstrated that sucrose promotes tumor progression dose-dependently. HDS also
contributes to heterochromatin reduction and severe tumor progression. Moreover,
we found that heterochromatin levels are important for tumor suppression as well as
the development and survival of tumor animals. Animals with overexpression and
knockdown of HP1 specifically in Ras/src-driven tumors show decreased tumor
growth and improved pupariation and eclosion. Increasing HP1 levels in the whole
tumor animal also promotes pupariation and eclosion rates, whereas reducing HP1
levels by half suppresses pupariation and eclosion rates. Interestingly, progression of
Ras/Src-transformed tumors exhibit a sex-specific “male-induced-demise” manner.
In addition, we found that heterochromatin levels are critical for glucose metabolism.
Finally, using expression profiling data and qRT-PCR, we identified several
metabolism-related genes that are regulated by HP1. Taken together, our study
suggests that heterochromatin levels play an important role in suppressing HDSinduced
tumor growth through the regulation of metabolism-related genes. A better
understanding of the molecular epigenetic mechanisms responsible for HDS-induced
tumor progression may provide new treatments for diet-induced metabolic diseases
and associated cancers.

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