Metastasis organotropism in colorectal cancer: advancing toward innovative therapies

He, Kai; Wang, Zhihan; Luo, Maochao; Li, Bowen; Ding, Ning; Li, Lei; He, Bo; Wang, Han; Cao, Jiangjun; Huang, Canhua; Yang, Jun; Chen, Hai-Ning

doi:10.1186/s12967-023-04460-5

Journal of Translational Medicine

Table 1 Targets for organotropic metastasis in this review

From: Metastasis organotropism in colorectal cancer: advancing toward innovative therapies

Organotropic site	Target	Role	Mechanism	Authors
Liver metastasis	GDH	Promotes	STAT3-mediated EMT induction	Liu et al. [43]
	GLS1	Promotes	HIF-1 promotes GLS1 expression	Xiang et al. [44]
	TPO	Promotes	TPO enhances hepatic metastasis of CD110 + TICs by activating lysine degradation	Wu et al. [45]
	FOXP3	Promotes	Potential to play a role in cancer progression and metastasis	Wang et al. [46]
	PDK1	Promotes	PDK1 knockdown increased reactive oxygen species	Qin et al. [47]
	ALDOB	Promotes	Metastatic cells in the liver upregulate the ALDOB, which enhances fructose metabolism	Bu et al. [48]
	PGI	Promotes	Overexpression of PGI contributes to the aggressive phenotype of human colon cancer	Tsutsumi et al. [49]
	SIRT2	Promotes	Liver metastasis involves IDH1 K224 hyperacetylation by inhibiting SIRT2 through HIF-1α-dependent SRC transcription, promoting invasion and migration	Wang et al. [50]
	PEPCK	Promotes	PCK1 enhances pyrimidine nucleotide production, which facilitates cancer cell Development in the context of hypoxia	Yamaguchi et al. [51]
	PKLR	Promotes	PKLR promotes cell survival in the tumor core in high cell density and hypoxia	Nguyen et al. [52]
	CKB	Promotes	By downregulating miR-483 and miR-551a, CKB release into the microenvironment is stimulated, promoting liver colonies	Loo et al. [53]
	GATM	Promotes	Elevated intratumoral creatine levels or GATM-mediated synthesis can enhance Slug and Snail expression via MPS1-activated Smad2/3, promoting liver metastasis	Zhang et al. [54]
	CXCR4	Promotes	Exosomes may promote colorectal cancer metastasis by recruiting CXCR4-expressing stromal cells to form a permissive metastatic microenvironment	Wang et al. [71]
	Exosomal HSPC111	Promotes	Mediated pre-metastatic niche formation	Zhang et al. [72]
	ITGαvβ5	Promotes	ITGαvβ5 preferentially adhered to Kupffer cells, enhancing hepatic tropism	Hoshino et al. [70]
	Exosomal miR-221/222	Promotes	Activates hepatic hepatocyte growth factor (HGF) in CRC exosome	Tian et al. [75]
	Exosomal miR-21-5p	Promotes	Caused a pro-inflammatory phenotype and liver metastasis of cancer via the miR-21-Toll-like receptor 7-IL-6 axis	Shao et al. [76]
	Fn-derived miR-1246,92b-3p,27a-3p	Promotes	Facilitate the liver metastasis of uninfected cells	Guo et al. [77]
	miR-139-3p miR-193a let-7 g	Promotes	Plasma exosomal was used to monitor CRC metastasis in real-time	Liu-cho et al. [78, 79]
	miR-253p,130b-3p,425-5p, 193a	Promotes	Potential to play a role in cancer progression and metastasis	Liu, Wanget al. [80, 81]
	Exosomal miR-934	Promotes	Enhanced M2 macrophage polarization in CRC cells by downregulating PTEN levels and activating the PI3K/AKT pathway	Li et al. [82]
	Exosomal miR-1246	Promotes	Mutant p53 CRC can transduce macrophages into M2-like macrophages with the help of exosomal miR-1246	Cooks et al. [113]
	HGF/cMet, PRL3, L1CAM, CXCR4, CAFs, Trop-2, ZFP57	Promotes	Those key candidate genes associated with colon cancer liver metastasis	Trusolino ~ Shoji et al. [148,149,150,151,152,153,154,155,156,157,158,159,160]
Lung metastasis	ACLY	Promotes	Increased expression of ACLY may enhance cell lipid production and lung metastasis	Wen et al. [56]
	SCD1	Promotes	Hyperglycemia-SCD1-MUFA caused CRC cell migration and invasion via PTEN regulation	Ran et al. [57]
	Glut3	Promotes	Stimulation of the Glut3-YAP signaling pathway acts as a master activator to change the cancer metabolism	Kuo et al. [58]
	BCKDK	Promotes	Phosphorylated BCKDK at the tyrosine 246 (Y246) site, enhancing CRC cell invasion	Tian et al. [59]
	HOXA13	Promotes	Expedited CRC lung metastasis via performing	Qiao et al. [60]
	Exosomes (MiR-25-3p MiR-106b-3p ITGBL1)	Promotes	CRC cells induce premetastatic niche formation by secreting exosomes to promote CRC lung metastasis	Song, Wang, Ji et al. [42, 83, 84]
	TAM secreting (TGF-β)	Promotes	Induces EMT by activating the Smad2/3/4 Snail pathway	Shen et al. [85]
	KRAS mutation	Promotes	Predisposition to lung metastasis	Kim,Tie,Cho et al. [161,162,163]
	REG1B, TGM6, NTF4, PNMA5, and HOXC13	Promotes	Those key candidate genes associated with colon cancer lung metastasis	Zhou et al. [164]
Peritoneal metastasis	CD44	Promotes	CD44-enriched vesicles induce the secretion of matrix metalloproteinases (MMPs), compromising mesothelial barrier integrity and facilitating cancer cell invasion	Nakamura et al. [87]
	α5β1 ADAM17	Promotes	Interactions between integrin α5β1 on CRC cells and its ligand ADAM17 on exosomes facilitate CRC-derived exosome binding and uptake, promoting cancer cell invasion	Cardenes et al. [88]
	MicroRNA-106b-5p	Promotes	MicroRNA-106b-5p promotes the polarization of M2 macrophages by inhibiting PDCD4, thereby mediating the metastasis of colorectal cancer (CRC) cells	Yang et al. [88, 89]
	Tumor-derived exosomes	Promotes	Exosomes may facilitate colorectal cancer peritoneal metastasis progression by modulating immune responses, including increased macrophage numbers and enhanced natural killer cell activation	Tokuda et al. [90]
	Tumor-derived exosomes	Promotes	Exosomes may undergo alterations during the peritoneal metastasis process, thereby influencing the tumor microenvironment and interactions	Vallejos et al. [91]
	IL-4, IL-10, TGF-β, M-CSF, andprostaglandin E2	Promotes	By promoting M2 cell polarization, tumor progression is mediated	Yin, Novak, Schreiber et al. [129,130,131]
	TGF-β, TNF-β, and IGF1	Promotes	By promoting CAFs, tumor progression is mediated	Koliaraki et al. [140]
	FBXW7	Inhibits	Inhibition of distant metastasis in colorectal cancer	Mlecnik, Stein, Stein et al. [165,166,167]
	MUC1	Promotes	By promoting epithelial-mesenchymal transition (EMT) while suppressing cell apoptosis	Schroeder et al. [169]
	TIMP-2, IGF-1, and HIF-1A	Promotes	Increased expression in clones of peritoneal metastasis from colorectal cancer	Lemoine, Varghese et al. [25, 170]
	CMS4 subtype	Promotes	Significant enrichment of CMS4 in primary tumors with peritoneal metastasis	Ubink, Laoukili et al. [171, 172]

Back to article page

ISSN: 1479-5876

Contact us

Submission enquiries: Access here and click Contact Us
General enquiries: info@biomedcentral.com