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结肠癌中粘蛋白及相关聚糖的机制和功能层面

Mechanistic and Functional Shades of Mucins and Associated Glycans in Colon Cancer.

作者信息

Pothuraju Ramesh, Krishn Shiv Ram, Gautam Shailendra K, Pai Priya, Ganguly Koelina, Chaudhary Sanjib, Rachagani Satyanarayana, Kaur Sukhwinder, Batra Surinder K

机构信息

Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE-68198, USA.

Fred and Pamela Buffett Cancer Center, University of Nebraska Medical Center, Omaha, NE-68105, USA.

出版信息

Cancers (Basel). 2020 Mar 11;12(3):649. doi: 10.3390/cancers12030649.

Abstract

Mucus serves as the chief protective barrier against pathogenic and mechanical insults in respiratory, gastrointestinal, and urogenital tracts. Altered mucin expression, the major component of mucus, in conjunction with differential glycosylation has been strongly associated with both benign and malignant pathologies of colon. Mucins and their associated glycans arbitrate their impact sterically as well as mechanically by altering molecular and microbial spectrum during pathogenesis. Mucin expression in normal and pathological conditions is regulated by nonspecific (dietary factors and gut microbiota) and specific (epigenetic and transcriptional) modulators. Further, recent studies highlight the impact of altering mucin glycome (cancer-associated carbohydrate antigens including Tn, Sialyl-Tn, Sialyl-Lew A, and Sialyl-Lewis X) on host immunomodulation, antitumor immunity, as well as gut microbiota. In light of emerging literature, the present review article digs into the impact of structural organization and of expressional and glycosylation alteration of mucin family members on benign and malignant pathologies of colorectal cancer.

摘要

黏液是呼吸道、胃肠道和泌尿生殖道抵御病原体和机械损伤的主要保护屏障。黏液的主要成分黏蛋白的表达改变,以及不同的糖基化作用,与结肠的良性和恶性病变都密切相关。在发病过程中,黏蛋白及其相关聚糖通过改变分子和微生物谱,在空间和机械方面发挥其作用。正常和病理条件下黏蛋白的表达受非特异性(饮食因素和肠道微生物群)和特异性(表观遗传和转录)调节剂的调控。此外,最近的研究强调了改变黏蛋白糖组(包括Tn、唾液酸化-Tn、唾液酸化-Lew A和唾液酸化-Lewis X等癌症相关碳水化合物抗原)对宿主免疫调节、抗肿瘤免疫以及肠道微生物群的影响。鉴于新出现的文献,本综述文章深入探讨了黏蛋白家族成员的结构组织、表达和糖基化改变对结直肠癌良性和恶性病变的影响。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/85b7/7139953/a274502caa54/cancers-12-00649-g001.jpg

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