High incidence (10.2%) and mortality (9.2%) rates led to the ranking of colorectal cancer (CRC) as the second most malignant tumor spectrum worldwide in 2020. Treatment strategies are becoming highly dependent on the molecular characteristics of CRC. The classical theories accept two models depicting the origin of CRC: The progression of adenoma to cancer and transformation from serrated polyps to cancer. However, the molecular mechanism of CRC development is very complex. For instance, CRCs originating from laterally spreading tumors (LST) do not adhere to any of these models and exhibit extremely serious progression and poor outcomes. In this article, we present another possible pathway involved in CRC development, particularly from LST, with important molecular characteristics, which would facilitate the design of a novel strategy for targeted therapy.

Colorectal cancer (CRC) is the third most prevalent malignancy worldwide. Laterally spreading tumors (LSTs), as special manifestations of digestive tract tumors, are often misdiagnosed or undiagnosed due to their unique morphological and pathological features. LST has no protruding lesions and progresses rapidly, and prognoses are consequently poor. LST progression to CRC is complicated. Clinical data indicate that the heart is rarely the site of primary tumorigenesis, and a class of atrial natriuretic peptides (ANPs) secreted by heart tissue play an important role in this phenomenon, which is closely related to the Wnt/β-catenin signaling pathway. However, previous studies focused solely on correlations between the Wnt/β-catenin signaling pathway, downstream gene expression and LST. Thus, correlational studies of ANP/ANP receptor, LST and CRC may be of great help in understanding the occurrence, development and treatment of LST, as well as in establishing specific and sensitive methods for detecting LST.