PLSCR1在基底样乳腺癌的作用与机制研究

基底样乳腺癌具有增殖活力高、侵袭力强、抗药性强、复发率高和转移能力强、生存率差等特征，是恶性程度最高的乳腺癌亚型。目前，基底样乳腺癌高侵袭力的调控机制尚不清楚。磷脂爬行酶1(Phospholipid scramblase 1, PLSCR1)是一种磷脂爬行酶，属于Ca2+结合的棕榈酰化II型膜蛋白。我们前期研究发现基底样乳腺癌细胞和组织样本的PLSCR1表达显著高于其它的亚型。此外，我们也发现PLSCR1与STAT1存在相互调控关系。在本申请项目中，我们将重点研究STAT1与PLSCR1两者相互调控的反馈环路，解析这一调控环路对基底样乳腺癌恶性演变的作用与机制，从体外和体内研究STAT1/PLSCR1与基底样乳腺癌的内在联系。本项目的开展将有助于为预防和治疗基底样乳腺癌提供理论依据和潜在标记分子。

Basal-like breast cancer (BLBC) is a subtype of breast cancer that associates with an aggressive clinical history, development of recurrence, distant metastasis, and shorter survival; however the molecular mechanisms underlying aggressiveness in BLBC are still unclear. Here, we found that overexpression of phospholipid scramblase 1 (PLSCR1), a Ca2+-dependent phospholipid scramblase, occurred specifically in BLBC and predicted poor prognosis in breast cancer patients. We also observed that STAT1 induced PLSCR1 expression, and PLSCR1 in turn upregulated STAT1 expression, forming a positive feedback loop between both molecules. The objective of this proposal is to explore the potential roles and mechanisms of PLSCR1 in tumorigenicity and metastasis of breast cancer cells. Elucidating the correlation between PLSCR1 and STAT1 will contribute to our understanding of how this positive feedback loop between both molecules controls tumorigenicity and metastasis in BLBC, providing potential prognostic and therapeutic targets for this disease.