Maintenance of gastrointestinal health is challenging as it requires balancing multifaceted processes within the highly complex and dynamic ecosystem of the gastrointestinal tract. Disturbances within this vibrant environment can have detrimental consequences, including the onset of gastrointestinal cancers. Globally, gastrointestinal cancers account for ~19% of all cancer cases and ~22.5% of all cancer-related deaths. Developing new ways to more readily detect and more efficiently target these malignancies are urgently needed. Whereas members of the tumour microenvironment, such as immune cells and fibroblasts, have already been in the spotlight as key players of cancer initiation and progression, the importance of the nervous system in gastrointestinal cancers has only been highlighted in the past few years. Although extrinsic innervations modulate gastrointestinal cancers, cells and signals from the gut's intrinsic innervation also have the ability to do so. Here, we shed light on this thriving field and discuss neural influences during gastrointestinal carcinogenesis. We focus on the interactions between neurons and components of the gastrointestinal tract and tumour microenvironment, on the neural signalling pathways involved, and how these factors affect the cancer hallmarks, and discuss the neural signatures in gastrointestinal cancers. Finally, we highlight neural-related therapies that have potential for the management of gastrointestinal cancers.

Tumor cells corrupt surrounding normal cells instructing them to support proliferative, pro-angiogenic and immunosuppressive networks that favor tumorigenesis and metastasis. This dynamic cross-talk is sustained by a range of intracellular signals and extracellular mediators produced by both tumoral and non-tumoral cells. Galectins -whether secreted or intracellularly expressed- play central roles in the tumorigenic process by delivering regulatory signals that contribute to reprogram fibroblasts, endothelial and immune cell programs. Through glycosylation-dependent or independent mechanisms, these endogenous lectins control a variety of cellular events leading to tumor cell proliferation, survival, migration, inflammation, angiogenesis and immune escape. Here we discuss the role of galectin-driven pathways, particularly those activated in non-tumoral stromal cells, in modulating tumor progression.

Gastrointestinal cancer is a group of tumors that affect multiple sites of the digestive system, including the stomach, liver, colon and pancreas. These cancers are very aggressive and rapidly metastasize, thus identifying effective targets is crucial for treatment. Galectin-1 (Gal-1) belongs to a family of glycan-binding proteins, or lectins, with the ability to cross-link specific glycoconjugates. A variety of biological activities have been attributed to Gal-1 at different steps of tumor progression. Herein, we summarize the current literature regarding the roles of Gal-1 in gastrointestinal malignancies. Accumulating evidence shows that Gal-1 is drastically up-regulated in human gastric cancer, hepatocellular carcinoma, colorectal cancer and pancreatic ductal adenocarcinoma tissues, both in tumor epithelial and tumor-associated stromal cells. Moreover, Gal-1 makes a crucial contribution to the pathogenesis of gastrointestinal malignancies, favoring tumor development, aggressiveness, metastasis, immunosuppression and angiogenesis. We also highlight that alterations in Gal-1-specific glycoepitopes may be relevant for gastrointestinal cancer progression. Despite the findings obtained so far, further functional studies are still required. Elucidating the precise molecular mechanisms modulated by Gal-1 underlying gastrointestinal tumor progression, might lead to the development of novel Gal-1-based diagnostic methods and/or therapies.