三陰性乳癌(TNBC)是一種具預後不良以及極高復發率的乳癌亞型，其特徵為缺乏動情激素受體(ER)、黃體激素受體(PR)以及人類表皮因子受體(HER2)之表達。目前三陰性乳癌仰賴化學療法，而抗藥性的產生是透過化療藥物根除癌細胞最主要的障礙。初級纖毛是突出細胞表面的胞器，它可以感測細胞外的物理及化學刺激，進而活化特定訊息途徑並活化下游基因表達。目前已有研究證實大多數癌細胞並不擁有初級纖毛，然而，初級纖毛生成在具抗藥性的癌細胞中可以被觀察到。鈣離子(Ca2+)在細胞訊息傳遞中扮演重要的角色，而鈣離子平衡失調已被證實與癌症發展有關，因此我們假設鈣離子參與三陰性乳癌細胞中初級纖毛所介導之化療抗藥性。在本研究中，我們將重點聚焦在細胞內鈣離子濃度是否會影響初級纖毛生成。我們發現ionomycin所引發的鈣離子內流能夠抑制纖毛生成，鈣離子螯合劑BAPTA-AM所造成的鈣離子濃度下降也能夠造成纖毛生成下調，而我們也發現鈣池操控鈣離子流(SOCE)可負調控纖毛生成。此外，透過光遺傳學工具調控鈣離子震盪波也可透過活化Aurora A進而下調纖毛生成水平。雖然在本研究中初級纖毛以及抗藥性之間的模糊關係尚未被釐清，我們的發現提供了纖毛生成可以被胞內鈣離子濃度調控的證據。

Triple-negative breast cancer (TNBC) is a breast cancer subtype with poor prognosis and high recurrence, which is characterized by lacking estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) expression. TNBC currently relies on chemotherapy treatment and the development of chemoresistance is a major obstacle to successfully eradicate cancer cells with chemotherapy. Primary cilium is an organelle protruding from the cell surface which can detect extracellular physical and chemical stimulations, activate specific signaling pathways and further activate downstream gene expression. Currently, some studies have verified that most cancer cells do not possess primary cilia; however, ciliogenesis can be observed in the cancer cells with chemoresistance. Calcium (Ca2+) plays an essential role in cellular signaling transduction. Ca2+ homeostasis dysregulation has already been verified to be associated with cancer development. We hypothesize that Ca2+ is involved in the primary cilia-mediated chemoresistance in TNBC cells. In this study, we focus on investigating whether cytosolic Ca2+ concentrations affect ciliogenesis. We found that ionomycin-induced Ca2+ influx suppressed ciliogenesis levels in TNBC cells and Ca2+ chelator BATPA-AM-induced Ca2+ depletion also caused ciliogenesis down-regulation. We also found that store-operated Ca2+ entry (SOCE) negatively regulated ciliogenesis. Furthermore, modulating Ca2+ oscillation by optogenetic tools also down-regulated ciliogenesis levels through Aurora A activation. Although the vague relationship between primary cilia and chemoresistance has not yet been determined in this study, our findings provide evidence that primary ciliogenesis can be regulated by manipulating intracellular Ca2+ concentration.

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