乳癌是2020年女性最常見的惡性腫瘤，也是全球女性癌症死亡的首要原因，Serine/threonine kinase 11 (STK11))是一種蛋白質激酶，STK11主要是去調控5' AMP-activated protein kinase (AMPK)的蛋白質激酶活性，進而去調控細胞凋亡、細胞代謝和細胞極性等功能，在先前的研究指出STK11是一種腫瘤抑制基因，它透過激活AMPK來抑制腫瘤細胞的生長和增殖，最近的研究發現在乳癌病人中發現有部分病人都帶有STK11突變，使得病人的腫瘤更加惡性，而先前研究中的數據表明腫瘤抑制基因除了可以去抑制腫瘤生長以外，還可以去影響到抗癌藥物的功能，例如:可以增強化療藥物的療效或是誘導腫瘤產生抗藥性，然而STK11在乳癌中對於藥物的影響機制仍未釐清，基於紫杉醇為目前是乳癌患者化療的常用的選擇之一，並且紫杉醇在部分乳癌病人中有著治療效果不佳情況，所以本研究想釐清STK11在乳癌中對紫杉醇療程的影響。為了研究STK11對紫杉醇療程的影響，我們使用細胞存活率分析來確定在乳癌細胞中的STK11缺失是否會影響紫杉醇治療的功效，而在實驗中我們觀察到相較於控制組，當沒有STK11的表現量時，會促進紫杉醇對乳癌細胞的治療效果。由於在先前研究中提及紫杉醇會藉由結合在微管上使得細胞無法有絲分裂，進而產生細胞凋亡。因此，為了確定STK11表現量的消失是否可以增強紫杉醇誘導的細胞凋亡作用，我們利用流式細胞術確定乳癌細胞的凋亡水平。我們觀察到在STK11缺失的乳癌細胞中，利用紫杉醇治療時會有更多的細胞凋亡現象。接著為了更進一步了解其中的機制，我們利用比較在紫杉醇治療下有無表現STK11乳癌細胞的RNA定序，分析了可能影響紫杉醇治療效果的相關基因。我們在Ingenuity Pathway Analysis (IPA)和Metacore分析中發現差異表達的基因皆與Rho GTPases家族有所相關，進而分析了參與的基因，並認為CDH5基因可能是影響STK11-KO乳癌細胞有著不同紫杉醇治療效果的潛在因素。最後我們在STK11-KO乳腺癌細胞中通過siRNA降低了CDH5的表達，並檢測了STK11-KO乳腺癌細胞中CDH5表現量和紫杉醇治療效果之間的關係，結果指出CDH5的表現量降低可能可以增強在STK11-KO乳癌細胞中紫杉醇的治療效果，因此本研究暗示STK11和CDH5可能是TNBC中提高紫杉醇敏感性的新生物標誌物及治療標的。

Breast cancer is the most common malignant tumor in females in 2020, and it is the first leading cause of cancer mortality in females around the world. Serine/threonine kinase 11 (STK11) is a protein kinase. STK11 mainly controls the activity of the 5' AMP-activated protein kinase (AMPK), which plays a role in various processes: apoptosis, cell metabolism, and cell polarity. STK11 is a tumor suppressor that inhibits growth and proliferation by activating AMPK. STK11 mutations have been identified in breast cancer patients and conferred tumor malignancy in the patient. Certain tumor suppressor genes can affect the therapeutic efficacy of cancer drugs, either enhancing the sensitivity to drugs or inducing the resistance to drugs. Paclitaxel (Taxol) is the major chemical drug for breast cancer patients, and the effect of tumor suppressor gene STK11 on Taxol is still largely unknown. Therefore, in this study, we will investigate whether the expression level of STK11 will affect the effectiveness of Taxol. Here, we used cell proliferation assay to determine the paclitaxel efficacy in mouse breast cancer cell lines. We found that deficiency of STK11 promoted sensitivity to paclitaxel treatment. Paclitaxel was known to interact with microtubules and caused cells unable to undergo mitosis, eventually leading to apoptosis. Hence, to determine whether STK11 knockout was prone to activate the apoptosis pathway by paclitaxel in breast cancer cells, we measured apoptosis levels by flow cytometry. We observed that more apoptotic cells were observed in STK11-knockout group during paclitaxel treatment. In order understand the downstream effects of paclitaxel, we analyzed paclitaxel sensitivity-related genes by total RNA sequencing (RNA-seq) in STK11 knockout cells. We found that differentially expressed genes were related to Rho family GTPases in Ingenuity Pathway Analysis (IPA) and Metacore analysis. Furthermore, the analysis suggested that the CDH5 gene was a potential genetic factor to influence the efficacy of Taxol treatment in STK11-KO breast cancer cells. Finally, we reduced the CDH5 expression through siRNA and examined the relationship between CDH5 and Taxol in STK11-KO breast cancer cells. The result demonstrated that knockdown of CDH5 could enhance the therapeutic effect of paclitaxel treatment in STK11-KO breast cancer cells. This study implied the STK11 and CDH5 might be novel biomarkers and therapeutic targets for improving paclitaxel sensitivity in TNBC.

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