Fujita Motomichi, Suzuki Hideo, Fukai Fumio
Department of Molecular Patho-Physiology, Tokyo University of Science, Noda 278-8510, Chiba, Japan.
Department of Gastroenterology, University of Tsukuba, Tsukuba 305-8575, Ibaraki, Japan.
World J Gastrointest Oncol. 2021 Sep 15;13(9):980-994. doi: 10.4251/wjgo.v13.i9.980.
Tenascin-C (TNC) is an adhesion modulatory protein present in the extracellular matrix that is highly expressed in several malignancies, including colon cancer. Although TNC is considered a negative prognostic factor for cancer patients, the substantial role of the TNC molecule in colorectal carcinogenesis and its malignant progression is poorly understood. We previously found that TNC has a cryptic functional site and that a TNC peptide containing this site, termed TNIIIA2, can potently and persistently activate beta1-integrins. In contrast, the peptide FNIII14, which contains a cryptic bioactive site within the fibronectin molecule, can inactivate beta1-integrins. This review presents the role of TNC in the development of colitis-associated colorectal cancer and in the malignant progression of colon cancer, particularly the major involvement of its cryptic functional site TNIIIA2. We propose new possible prophylactic and therapeutic strategies based on inhibition of the TNIIIA2-induced beta1-integrin activation by peptide FNIII14.
腱生蛋白-C（TNC）是一种存在于细胞外基质中的黏附调节蛋白，在包括结肠癌在内的多种恶性肿瘤中高表达。尽管TNC被认为是癌症患者的不良预后因素，但TNC分子在结直肠癌发生及其恶性进展中的重要作用仍知之甚少。我们先前发现TNC有一个隐蔽功能位点，包含该位点的TNC肽（称为TNIIIA2）可有效且持续地激活β1整合素。相反，纤连蛋白分子中包含一个隐蔽生物活性位点的肽FNIII14可使β1整合素失活。本综述介绍了TNC在结肠炎相关结直肠癌发生及结肠癌恶性进展中的作用，特别是其隐蔽功能位点TNIIIA2的主要作用。我们基于肽FNIII14对TNIIIA2诱导的β1整合素激活的抑制作用，提出了新的可能的预防和治疗策略。
