缝隙连接蛋白43对细胞外基质的调控作用机制及其生物学意义的研究

Extracellular matrix (ECM), serve as the major components of tumor microenvironment, play a critical role in tumor invasion and metastasis, but the mechanism underling ECM regulation is not clear. Connexin (Cx) proteins, which form gap junction (GJ) channels, are closely related with several pathological process of tumor. However, many of the mechanisms have not been fully understood. A recent study demonstrated that after 9 days of healing, the speed of wound healing in the Cx43 mutant G60S mice were significantly slower than which in the WT mice. Since the important role of ECM in wound healing has been well known, we hypothesize that Cx43 is a critical mechanism which is involved in the regulation of ECM components. To investigate this hypothesis, we will use immunofluorescence, western-blot, ELISA, [35S]-methionine labeling, co-immunoprecipitation and other methods to investigate the role and mechanism of Cx43 in the synthesis and degradation of ECM components at cell and tissue level, thereby revealing the critical role and significance of Cx43 in tumor invasion and metastasis. This project will provide a novel theory for cancer therapy and contribute to the development of new antitumor drugs.

细胞外基质（ECM）作为肿瘤细胞生长微环境的主要组分，在肿瘤的侵袭与转移过程中发挥重要的作用,但目前对其调控机制尚缺乏研究。细胞间缝隙连接（GJ）的构成蛋白（Cx）与肿瘤细胞的多种病理过程密切相关，然而其中的机制仍有待进一步阐明。在前期的研究中，我们发现了Cx43基因G60S突变的小鼠皮肤伤口愈合速度明显慢于正常对照组小鼠。鉴于ECM在皮肤修复及伤口愈合中的重要作用，我们提出假设：Cx43很可能是参与调节ECM主要成分的重要机制。为证明这一科学假设，我们拟从细胞、动物水平，采用免疫荧光染色、Western-blot法 、ELISA法、[35S]同位素标记法、Zymography法、免疫共沉淀法等技术，深入探讨Cx43在ECM主要组分合成、降解过程中的作用及调控机制，从而揭示Cx43在肿瘤细胞侵袭、转移过程中的重要作用及意义，将有助于创新和开发新的肿瘤药物及治疗工具，以控制肿瘤的侵袭和转移。