Molecular targets and pathways involved in liver metastasis of colorectal cancer

Abstract

We here summarize the current view of molecular mechanisms involved in the dissemination process of colorectal cancer cells to the liver as deduced from preclinical models. We focus on molecular aspects of the current understanding of the biology of liver metastases formation and survival, both being crucial for identification and validation of possible therapeutic targets and review the latest findings elucidating some features of the liver as a metastatic niche. In more detail, we outline the role of proteases and of major pathways such asc-MET signaling and its modulation by factors such as MACC1 and TIMP1, as well as Notch and TGFβ signaling. The relevance of these signalling pathways during tumor-stroma interactions in this context will be addressed. In addition, the functional role and validation of targets such as PRL3, Trop-2, L1CAM, S100A4, S100P, CD133, LIPC, and APOBEC3G are summarized.

Peripheral blood leucocytes show differential expression of tumour progression‐related genes in colorectal cancer patients who have a postoperative intra‐abdominal infection: a prospective matched cohort study

“…Although we cannot establish a direct causal link between those previous functional studies and our present results, the gene expression patterns obtained point to circulating blood leucocytes as one plausible source of the pro-angiogenic and pro-tumourigenic systemic environment. Our present results also provide some candidates for mediating the stimulation of cancer cell invasiveness, such as S100P, HGF, MMP9 and ADAM9 [29], which were found to be upregulated in the group of patients with infection. Moreover, our previous investigations suggested that the inflammatory reaction in response to infection leads to an increased expression of local and circulating pro-angiogenic factors, particularly vascular endothelial growth factor (VEGF), which might also facilitate the growth of residual tumour cells [14].…”

CD44v6-competent tumor exosomes promote motility, invasion and cancer-initiating cell marker expression in pancreatic and colorectal cancer cells

“…Low TIMP1 and PAI1 expression in CD44v6 kd cells deserves further elaboration. Low PAI1 [81] and TIMP1 [82] expression can contribute to loss of invasion. However, TIMP1 may also promote metastases by preserving MET expression and PI3K/Akt activation and promoting HIF1α and miR-210 upregulation, which both require cooperation with the tetraspanin CD63 [83].…”

Development of novel predictive miRNA/target gene pathways for colorectal cancer distance metastasis to the liver using a bioinformatic approach

“…Our study demonstrated that during metastasis, there is an interaction of different pathways that involve different genes. A previous study established that CRC progression to liver colonization involves extracellular matrix organization [72,73], and another study established that IGF regulation is also involved [74,75]. We showed that the interaction of extracellular matrix organization, regulation of IGFs and IGBPs, signal transduction and the immune system pathways result in CRC metastasis to the liver.…”