Molecular alterations of cancer cell and tumour microenvironment in metastatic gastric cancer

Abstract

The term metastasis is widely used to describe the endpoint of the process by which tumour cells spread from the primary location to an anatomically distant site. Achieving successful dissemination is dependent not only on the molecular alterations of the cancer cells themselves, but also on the microenvironment through which they encounter. Here, we reviewed the molecular alterations of metastatic gastric cancer (GC) as it reflects a large proportion of GC patients currently seen in clinic. We hope that further exploration and understanding of the multistep metastatic cascade will yield novel therapeutic targets that will lead to better patient outcomes.

Fig. 1

Metastatic routes and sites in gastric cancer. Major routes of distant metastasis in gastric cancer: intraperitoneal, lymphatic and haematogenous spread, and direct invasion into neighbouring organs. Common sites of metastases: spleen, pancreas, colon, liver, peritoneum, ovary, lymph nodes, lung and bone

Fig. 2

Epithelial–mesenchymal transition and tumour–stromal interactions in gastric cancer. Main phenotypic changes of EMT in gastric cancer include loss of cell polarity, degradation of cell-anchoring junctions, cytoskeleton changes, acquisition of invasiveness and ultimately degradation of basement membrane. Interactions within between key components of the stromal environment. EMT epithelial–mesenchymal transition, ECM extracellular matrix, CAF cancer-associated fibroblast, MSC mesenchymal stem cell, MMP matrix metalloproteinase

Fig. 3

Molecular mechanisms of EMT in gastric cancer. Major signalling pathways that regulate EMT in gastric cancer. PI3K/AKT, WNT/β-Catenin, ERK, TGF-β/SMAD and Snail signalling pathways promote EMT; Notch1/2 inhibits EMT in gastric cancer