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黏蛋白糖蛋白:癌症治疗的潜在生物标志物和分子靶点。

MUC Glycoproteins: Potential Biomarkers and Molecular Targets for Cancer Therapy.

机构信息

Department of Pharmacognosy, Amrita School of Pharmacy, Amrita Vishwa Vidyapeetham, AIMS Health Science Campus, Ponekkara P. O., Kochi, Kerala 682041, India.

出版信息

Curr Cancer Drug Targets. 2021;21(2):132-152. doi: 10.2174/1568009620666201116113334.

DOI:10.2174/1568009620666201116113334
PMID:33200711
Abstract

MUC proteins have great significance as prognostic and diagnostic markers as well as a potential target for therapeutic interventions in most cancers of glandular epithelial origin. These are high molecular weight glycosylated proteins located in the epithelial lining of several tissues and ducts. Mucins belong to a heterogeneous group of large O-glycoproteins that can be either secreted or membrane-bound. Glycosylation, a post-translational modification affects the biophysical, functional and biochemical properties and provides structural complexity for these proteins. Aberrant expression and glycosylation of mucins contribute to tumour survival and proliferation in many cancers, which in turn activates numerous signalling pathways such as NF-kB, ERα, HIF, MAPK, p53, c-Src, Wnt and JAK-STAT, etc. This subsequently induces cancer cell growth, proliferation and metastasis. The present review mainly demonstrates the functional aspects of MUC glycoproteins along with its unique signalling mechanism and role of aberrant glycosylation in cancer progression and therapeutics. The importance of MUC proteins and its subtypes in a wide spectrum of cancers including but not limited to breast cancer, colorectal cancer, endometrial and cervical cancer, lung cancer, primary liver cancer, pancreatic cancer, prostate cancer and ovarian cancer has been exemplified with significance in targeting the same. Several patents associated with the MUC proteins in the field of cancer therapy are also emphasized in the current review.

摘要

黏蛋白作为大多数腺体上皮来源的癌症的预后和诊断标志物以及治疗干预的潜在靶点具有重要意义。这些是位于几种组织和导管的上皮衬里的高分子量糖基化蛋白。黏蛋白属于一组异质的大型 O-糖蛋白,既可以分泌也可以膜结合。糖基化是一种翻译后修饰,影响这些蛋白质的物理、功能和生化特性,并为其提供结构复杂性。黏蛋白的异常表达和糖基化有助于许多癌症中的肿瘤存活和增殖,这反过来又激活了许多信号通路,如 NF-kB、ERα、HIF、MAPK、p53、c-Src、Wnt 和 JAK-STAT 等。这继而诱导癌细胞生长、增殖和转移。本综述主要展示了 MUC 糖蛋白的功能方面及其独特的信号机制以及异常糖基化在癌症进展和治疗中的作用。MUC 蛋白及其亚型在广泛的癌症中具有重要意义,包括但不限于乳腺癌、结直肠癌、子宫内膜癌和宫颈癌、肺癌、原发性肝癌、胰腺癌、前列腺癌和卵巢癌,在针对这些癌症的治疗中具有重要意义。目前的综述还强调了与癌症治疗领域的 MUC 蛋白相关的几项专利。

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