Stem Cell Biology Laboratory, Department of Genetic Engineering, School of Bioengineering, Faculty of Engineering and Technology, SRM Institute of Science and Technology, Kanchipuram, Kattankulathur, Chennai, Tamil Nadu, 603203, India.
College of Human and Human Sciences, Charles Darwin University, Ellangowan Drive, Darwin, Northern Territory, 0909, Australia.
Cell Oncol (Dordr). 2021 Jun;44(3):473-494. doi: 10.1007/s13402-021-00591-3. Epub 2021 Mar 11.
Oral squamous cell carcinoma (OSCC) is a malignant oral cavity neoplasm that affects many people, especially in developing countries. Despite several advances that have been made in diagnosis and treatment, the morbidity and mortality rates due to OSCC remain high. Accumulating evidence indicates that aberrant activation of cellular signaling pathways, such as the Notch, Wnt and Hedgehog pathways, occurs during the development and metastasis of OSCC. In this review, we have articulated the roles of the Notch, Wnt and Hedgehog signaling pathways in OSCC and their crosstalk during tumor development and progression. We have also examined possible interactions and associations between these pathways and treatment regimens that could be employed to effectively tackle OSCC and/or prevent its recurrence.
Activation of the Notch signaling pathway upregulates the expression of several genes, including c-Myc, β-catenin, NF-κB and Shh. Associations between the Notch signaling pathway and other pathways have been shown to enhance OSCC tumor aggressiveness. Crosstalk between these pathways supports the maintenance of cancer stem cells (CSCs) and regulates OSCC cell motility. Thus, application of compounds that block these pathways may be a valid strategy to treat OSCC. Such compounds have already been employed in other types of cancer and could be repurposed for OSCC.
口腔鳞状细胞癌（OSCC）是一种恶性口腔肿瘤，影响了许多人，尤其是在发展中国家。尽管在诊断和治疗方面取得了一些进展，但 OSCC 的发病率和死亡率仍然很高。越来越多的证据表明，细胞信号通路的异常激活，如 Notch、Wnt 和 Hedgehog 通路，发生在 OSCC 的发展和转移过程中。在这篇综述中，我们阐述了 Notch、Wnt 和 Hedgehog 信号通路在 OSCC 中的作用及其在肿瘤发生和进展过程中的相互作用。我们还研究了这些通路与治疗方案之间可能存在的相互作用和关联，这些关联可能被用来有效地治疗 OSCC 和/或预防其复发。
Notch 信号通路的激活上调了包括 c-Myc、β-catenin、NF-κB 和 Shh 在内的几个基因的表达。Notch 信号通路与其他通路之间的关联已被证明可以增强 OSCC 肿瘤的侵袭性。这些通路之间的串扰支持癌症干细胞（CSCs）的维持，并调节 OSCC 细胞的迁移。因此，应用阻断这些通路的化合物可能是治疗 OSCC 的有效策略。这些化合物已经在其他类型的癌症中得到应用，并可以重新用于 OSCC。
