卵巢癌（OC）是最致命的妇科恶性肿瘤，由于其无症状、化疗耐药和复发而具有很高的死亡率。然而，这些现象背后的适当机制知识仍然不足。由于癌症干细胞也表现出化疗耐药性，因此经常观察到癌症复发。我们的目的是破译 OC 化学耐药性和干性背后的分子机制。早期研究表明，PITX2（一种同源盒转录因子）及其不同亚型通过调节不同的信号通路与 OC 进展相关。此外，它们还调节肾癌和结肠癌中药物外流转运蛋白的表达，从而赋予肿瘤细胞化学抗性。考虑到这些背景，我们决定寻找 PITX2 同工型在促进 OC 细胞干细胞性和化疗耐药性中的作用。在这项研究中，PITX2A/B 已被证明可以促进干性并增强 ABCB1 的转录。研究发现 PITX2 通过直接结合 ABCB1 的启动子来增强 ABCB1 基因的表达。为了进一步研究PITX2基因表达的调控机制，我们发现TGFβ信号传导可以通过SMAD和非SMAD信号传导途径增强PITX2A/B的表达。总的来说，我们得出结论，TGFβ1 激活的 PITX2A/B 在 OC 细胞中诱导干细胞样特征和化学抗性特性。

Ovarian cancer (OC) is the deadliest gynecological malignancy, having a high mortality rate due to its asymptomatic nature, chemoresistance and recurrence. However, the proper mechanistic knowledge behind these phenomena is still inadequate. Cancer recurrence is commonly observed due to cancer stem cells which also show chemoresistance. We aimed to decipher the molecular mechanism behind chemoresistance and stemness in OC. Earlier studies suggested that PITX2, a homeobox transcription factor and its different isoforms are associated with OC progression upon regulating different signaling pathways. Moreover, they regulate the expression of drug efflux transporters in kidney and colon cancer, rendering chemoresistance properties in the tumor cell. Considering these backgrounds, we decided to look for the role of PITX2 isoforms in promoting stemness and chemoresistance in OC cells. In this study, PITX2A/B has been shown to promote stemness and to enhance the transcription of ABCB1. PITX2 has been discovered to augment ABCB1 gene expression by directly binding to its promoter. To further investigate the regulatory mechanism of PITX2 gene expression, we found that TGFβ signaling could augment the PITX2A/B expression through both SMAD and non-SMAD signaling pathways. Collectively, we conclude that TGFβ1-activated PITX2A/B induces stem-like features and chemoresistance properties in the OC cells.