Hombach-Klonisch Sabine, Natarajan Suchitra, Thanasupawat Thatchawan, Medapati Manoj, Pathak Alok, Ghavami Saeid, Klonisch Thomas
Department of Human Anatomy and Cell Science, University of Manitoba , Winnipeg, MB , Canada ; Department of Obstetrics, Gynecology and Reproductive Sciences, University of Manitoba , Winnipeg, MB , Canada.
Department of Human Anatomy and Cell Science, University of Manitoba , Winnipeg, MB , Canada.
Front Endocrinol (Lausanne). 2014 Mar 25;5:37. doi: 10.3389/fendo.2014.00037. eCollection 2014.
The two main reasons for death of cancer patients, tumor recurrence and metastasis, are multi-stage cellular processes that involve increased cell plasticity and coincide with elevated resistance to anti-cancer treatments. Epithelial-to-mesenchymal transition (EMT) is a key contributor to metastasis in many cancer types, including thyroid cancer and is known to confer stem cell-like properties onto cancer cells. This review provides an overview of molecular mechanisms and factors known to contribute to cancer cell plasticity and capable of enhancing cancer cell resistance to radio- and chemotherapy. We elucidate the role of DNA repair mechanisms in contributing to therapeutic resistance, with a special emphasis on thyroid cancer. Next, we explore the emerging roles of autophagy and damage-associated molecular pattern responses in EMT and chemoresistance in tumor cells. Finally, we demonstrate how cancer cells, including thyroid cancer cells, can highjack the oncofetal nucleoprotein high-mobility group A2 to gain increased transformative cell plasticity, prevent apoptosis, and enhance metastasis of chemoresistant tumor cells.
癌症患者死亡的两个主要原因，即肿瘤复发和转移，是多阶段的细胞过程，涉及细胞可塑性增加，且与抗癌治疗耐药性升高同时出现。上皮-间质转化（EMT）是包括甲状腺癌在内的多种癌症类型中转移的关键促成因素，已知其赋予癌细胞干细胞样特性。本综述概述了已知有助于癌细胞可塑性并能增强癌细胞对放疗和化疗耐药性的分子机制和因素。我们阐明了DNA修复机制在导致治疗耐药性中的作用，特别强调了甲状腺癌。接下来，我们探讨自噬和损伤相关分子模式反应在肿瘤细胞EMT和化疗耐药性中的新作用。最后，我们展示了癌细胞，包括甲状腺癌细胞，如何劫持癌胚核蛋白高迁移率族A2以获得更高的转化细胞可塑性、防止细胞凋亡并增强化疗耐药肿瘤细胞的转移。
