Rasool Shelan, Hussein Zihel, Ali Hazhmat, Al Ismaeel Qais, Al-Mahmoodi Hanaa, Yalda Mayada, Najeeb Hishyar
College of Medicine, University of Duhok, Duhok, Iraq.
College of Biotechnology, Al-Nahrain University, Baghdad, Iraq .
Cell Mol Biol (Noisy-le-grand). 2024 Nov 27;70(11):134-143. doi: 10.14715/cmb/2024.70.11.20.
Colorectal cancer (CRC) is the third most frequent type of cancer and the second leading cause of cancer-related deaths globally. Despite a thorough understanding of its biology, etiology, and epidemiology, an estimated 1.8 million new cases are diagnosed each year, and 900000 people die as a result of malignancy. The current study aims to investigate the expression pattern of S100A4 and S100A14 proteins in CRC tissue specimens and a panel of cell lines. Furthermore, to explore the metastatic potential of the aforementioned proteins in relation to the epithelial-mesenchymal transition and their possible association with the clinical features of CRC. The present study involved 80 patients diagnosed with CRC. Upon identification of the sociodemographic and clinicopathological features of the participants, immunohistochemical studies were conducted to measure the expression pattern of the S100 proteins in CRC tissues. In addition to qPCR and western blot studies, a series of in vitro experiments were conducted in a panel of CRC cell lines to assess the effects of S100 protein expression in cell migration, invasion, and proliferation. The number of CRC patients with high S100A4 expression levels was considerably higher than those with low expression (p < 0.0001). S100A4 is positively correlated with TNM staging, nodal metastasis, distant metastasis, and perineural invasion and was statistically significant (p = 0.02, 0.01, 0.0001, and 0.02, respectively). In vitro studies demonstrated that S100A14 knockdown induced EMT and resulted in a substantial increase in cell proliferation, migration, and invasion in HT29 cells. Moreover, S100A4 knockdown substantially inhibited migration, invasion, and proliferation in LoVo cells. The findings collectively suggest that both S100A4 and S100A14 play a pivotal role in colorectal cancer progression. Overexpression of S100A4 consistently with S100A14 downregulation is associated with the activation of epithelial-mesenchymal transition, which in turn enhances cell proliferation, migration, and invasion.
结直肠癌（CRC）是全球第三大常见癌症类型，也是癌症相关死亡的第二大主要原因。尽管对其生物学、病因学和流行病学有了深入了解，但每年估计仍有180万新病例被诊断出来，90万人死于恶性肿瘤。本研究旨在调查S100A4和S100A14蛋白在结直肠癌组织标本和一组细胞系中的表达模式。此外，探讨上述蛋白与上皮-间质转化相关的转移潜能及其与结直肠癌临床特征的可能关联。本研究纳入了80例诊断为结直肠癌的患者。在确定参与者的社会人口统计学和临床病理特征后，进行免疫组织化学研究以测量S100蛋白在结直肠癌组织中的表达模式。除了qPCR和蛋白质印迹研究外，还在一组结直肠癌细胞系中进行了一系列体外实验，以评估S100蛋白表达对细胞迁移、侵袭和增殖的影响。S100A4表达水平高的结直肠癌患者数量明显高于低表达患者（p < 0.0001）。S100A4与TNM分期、淋巴结转移、远处转移和神经周围浸润呈正相关，且具有统计学意义（分别为p = 0.02、0.01、0.0001和0.02）。体外研究表明，S100A14基因敲低诱导上皮-间质转化，并导致HT29细胞的细胞增殖、迁移和侵袭大幅增加。此外，S100A4基因敲低显著抑制LoVo细胞的迁移、侵袭和增殖。这些发现共同表明，S100A4和S100A14在结直肠癌进展中都起着关键作用。S100A4的过表达与S100A14的下调一致，与上皮-间质转化的激活相关，进而增强细胞增殖、迁移和侵袭。
