Published online Apr 28, 2023. doi: 10.3748/wjg.v29.i16.2359
Peer-review started: October 19, 2022
First decision: December 12, 2022
Revised: December 17, 2022
Accepted: April 7, 2023
Article in press: April 7, 2023
Published online: April 28, 2023
Processing time: 187 Days and 5.3 Hours
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.
Core Tip: Although laterally spreading tumors (LST) are considered vital precancerous lesions of colorectal cancer (CRC), the mechanism mediating their transition to CRC development is unclear. Adenomatous polyposis coli (APC)-truncating mutations driven by Golgi fragmentation are very important cellular events that can abrogate the microtubule binding properties of APC. This effect reduces the stability of microtubules, impacts cell proliferation and survival, causes chromosomal instability, and increases migration. Downstream characteristics of Golgi fragmentation indicate alterations in Ataxia-telangiectasia mutated and anoctamin 5 expression, whereas their gene expression changes are significant in LST. This implies a novel pathway for CRC development from LST.