Ancer statistics in 2020, 19.3 million new instances had been diagnosed and cancer contributed to ten.0 million deaths1. Consequently, cancer is becoming one of probably the most critical troubles which threaten public health. The most striking attributes of cancer are uncontrolled proliferation, regional invasion, and distant metastasis. Nowadays, the mainstream therapies for cancer treatment contain surgery, chemotherapy, radiotherapy, targeted therapy, and immunotherapy. Cancer-related death is mainly triggered by tumor recurrence and distant metastasis after systemic antitumor treatment. Although great advances happen to be accomplished for cancer remedy in recent years, specially within the field of targeted therapy and immune therapy, the pursuit for converting this life-threatening illness into a manageable chronic condition has never stopped. The extensive understanding of cancer cells, also because the microenvironment supporting the malignant behavior of cancer cells, are of equal significance for developing novel therapeutics against cancer. The extracellular matrix (ECM), which comprises the interstitial components inside tissues or organs for all metazoan organisms, plays important roles for all biological processes by giving architectural help, anchorage for cell adhesion, a reservoir for water, and numerous growth things, as well as inductions for intracellular Endothelin R Type B (EDNRB) Proteins Storage & Stability signaling pathways. In accordance with a complete study utilizing both proteomic analyses on the in vivo ECM composition and in SHP-2 Proteins Recombinant Proteins silico prediction2, 278 genes were identified ascore elements of the “matrisome” for humans, accounting for 1 on the complete proteome. Ever since the identification and characterization of collagen, by far the most abundant component of ECM, inside the 1930s, the complicated network of ECM began to be gradually revealed via contemporary biochemistry methods3. Most of the proteins within the ECM is usually classified into two groups, fibrous proteins, and glycosaminoglycan. The former consist of collagen, fibronectin, elastin, and laminin, and also the latter primarily consists of hyaluronic acid, chondroitin sulfate, keratan sulfate, and heparan sulfate. These molecules are crosslinked and distributed heavily within the ECM, forming the mesh structure for tissues. As early as the 1970s, the important roles of ECM within the determination of cell morphology and responses to development factors had been proven with strong empirical evidence4. Then the pursuit of discovering the intermembrane signal transducers linking ECM and intercellular signaling pathways developed a lot of fantastic works marked by the identification of integrins in 1980s5. Ever since then, the field of ECM ell interaction developed rapidly, plus the vast signaling network bridging extracellular environment and complicated cell behaviors started to reveal itself progressively as a result of continuous efforts of researchers and technological advances. During the 2010s, the clinical application of Ibrutinib (a small molecular compound inhibiting integrin signaling) for the treatment of lymphoid leukemia and lymphoma was a hallmark occasion for the productive translation of biological knowledge to sensible medicines within this research area10,11. In the exact same time, bioengineering of artificial and natural ECM materials also achieved excellent success in multiple branches of medicine, which include osteology,1 Division of Hepatobiliary and Pancreatic Surgery, Division of Surgery, Very first Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, China; 2School of Med.