Exploring the role of sporadic BRAF and KRAS mutations during colorectal cancer pathogenesis: A spotlight on the contribution of the endosome-lysosome system

Jingying Tang, Giang T. Lam, Robert D. Brooks, Mark Miles, Zivile Useckaite, Ian RD. Johnson , Ben S-Y Ung, Carmela Martini, Litsa Karageorgos, Shane M. Hickey, Stavros Selemidis, Ashley Hopkins, Andrew Rowland, Ryash Vather , John J. O'Leary, Douglas Brooks, Maria Caruso, Jessica M. Logan

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Abstract

The highly heterogenous nature of colorectal cancer can significantly hinder its early and accurate diagnosis, eventually contributing to high mortality rates. The adenoma-carcinoma sequence and serrated polyp-carcinoma sequence are the two most common sequences in sporadic colorectal cancer. Genetic alterations in adenomatous polyposis coli (APC), v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) and tumour protein 53 (TP53) genes are critical in adenoma-carcinoma sequence, whereas v-Raf murine sarcoma viral oncogene homolog B (BRAF) and MutL Homolog1 (MLH1) are driving oncogenes in the serrated polyp-carcinoma sequence.

Sporadic mutations in these genes contribute differently to colorectal cancer pathogenesis by introducing distinct alterations in several signalling pathways that rely on the endosome-lysosome system. Unsurprisingly, the endosome-lysosome system plays a pivotal role in the hallmarks of cancer and contributes to specialised colon function. Thus, the endosome-lysosome system might be distinctively influenced by different mutations and these alterations may contribute to the heterogenous nature of sporadic colorectal cancer. This review highlights potential connections between major sporadic colorectal cancer mutations and the diverse pathogenic mechanisms driven by the endosome-lysosome system in colorectal carcinogenesis.
Original languageEnglish
Article number216639
Number of pages9
JournalCancer Letters
Volume585
Early online date28 Jan 2024
DOIs
Publication statusPublished - 31 Mar 2024

Keywords

  • CRC
  • Pathogenesis
  • BRAF
  • KRAS
  • Endosome-lysosome

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