High extracellular matrix stiffness upregulates TNNT1 to awaken dormant tumor cells in liver metastatic niches of gastric cancer

Liver is one of the target organs bearing the most frequent distant metastasis of gastric cancer (GC), and patients with GC liver metastasis suffering from poor prognosis. According to "seed and soil" theory, important and complex interactions between disseminated tumor cells (DTCs) and metastasis tumor microenvironment (MTM) have played a vital role in waking the dormant DTCs and promoting their proliferation. We have discovered that the aberrantly activated cancer associated fibroblasts (CAFs) could significantly increase the enrichment and stiffness of extracellular matrix (ECM). ECM with high stiffness could facilitate the accumulation of Troponin T1, slow skeletal type (TNNT1) in cytoplasm for dormant DTCs awaking and proliferation. We set off from observing the stiffness of ECM around liver metastatic niches of GC and performed in vivo and in vitro study for further study. Based on the gained information, we plan to further unveil the underlying mechanism and explore the clinical transformation value using the ex-vivo and patient derived xenograft (PDX) model. Our study aims to illustrate the relationship between ECM stiffness and tumor dormancy awakening in liver metastasis of GC and provide reliable theoretical and research basis for treatment of GC liver metastasis.