Appunni Sandeep, Rubens Muni, Ramamoorthy Venkataraghavan, Anand Vivek, Khandelwal Madhuram, Saxena Anshul, McGranaghan Peter, Odia Yazmin, Kotecha Rupesh, Sharma Alpana
All India Institute of Medical Sciences, New Delhi, India; Government Medical College, Kozhikode, Kerala, India.
Miami Cancer Institute, Miami, FL, USA.
Clin Chim Acta. 2021 Mar;514:1-7. doi: 10.1016/j.cca.2020.12.011. Epub 2020 Dec 15.
The extracellular matrix (ECM) consists of a myriad of structural and signaling molecules which potentially regulate cell function and homeostasis. Lumican, a class II SLRP (small leucine rich proteoglycan) is a ubiquitous ECM component which not only organizes the collagen based structural matrix, but also modulates cell proliferation signals as observed in cancer. In the perspective of cancer biology, lumican expression in the tumor microenvironment is associated with signaling, which can result in either pro-tumorigenic or anti-tumorigenic effects. Its pro-tumorigenic effects are mainly observed in gastric, bladder and liver cancers, which is associated with deterioration of clinical prognosis. Lumican mediated pro-tumorigenic effects involve activation of focal adhesion kinases (FAK), mitogen activated protein kinases (MAPK) and metalloproteinase-9 (MMP-9). On the contrary, in breast cancer, pancreatic cancer and melanoma, lumican demonstrates anti-tumorigenic effects, which are associated with favorable clinical outcomes. Anti-tumorigenic potential of lumican is clubbed with epithelial-mesenchymal transition reprogramming as well as downregulation of extracellular signal-regulated kinases (ERK), FAK and MMP-14 mediated pathways thereby preventing tumorigenesis. This review highlights that the expressional significance of lumican in cancer biogenesis is tumor specific and demands rigorous cancer-specific evaluation to understand its role as a potential anti-cancer target or a therapeutic molecule.
细胞外基质（ECM）由无数结构和信号分子组成，这些分子可能调节细胞功能和内环境稳定。核心蛋白聚糖是一种II类富含亮氨酸小分子蛋白聚糖（SLRP），是一种普遍存在的细胞外基质成分，它不仅能构建基于胶原蛋白的结构基质，还能调节癌症中观察到的细胞增殖信号。从癌症生物学的角度来看，肿瘤微环境中核心蛋白聚糖的表达与信号传导有关，这可能导致促肿瘤或抗肿瘤作用。其促肿瘤作用主要在胃癌、膀胱癌和肝癌中观察到，这与临床预后恶化有关。核心蛋白聚糖介导的促肿瘤作用涉及粘着斑激酶（FAK）、丝裂原活化蛋白激酶（MAPK）和基质金属蛋白酶-9（MMP-9）的激活。相反，在乳腺癌、胰腺癌和黑色素瘤中，核心蛋白聚糖表现出抗肿瘤作用，这与良好的临床结果相关。核心蛋白聚糖的抗肿瘤潜力与上皮-间质转化重编程以及细胞外信号调节激酶（ERK）、FAK和MMP-14介导的信号通路下调有关，从而预防肿瘤发生。本综述强调，核心蛋白聚糖在癌症发生中的表达意义具有肿瘤特异性，需要进行严格的癌症特异性评估，以了解其作为潜在抗癌靶点或治疗分子的作用。
