Colorectal Liver Metastasis: Molecular Mechanism and Interventional Therapy

Overview

Journal Signal Transduct Target Ther

Specialties Cell Biology
Pharmacology

Date 2022 Mar 5

PMID 35246503

Authors

Hui Zhou

Zhongtao Liu

Yongxiang Wang

Xiaoyong Wen

Eric H Amador

Liqin Yuan

Xin Ran

Li Xiong

Yuping Ran

Wei Chen

Yu Wen

Affiliations

Soon will be listed here.

Abstract

Colorectal cancer (CRC) is one of the most frequently occurring malignancy tumors with a high morbidity additionally, CRC patients may develop liver metastasis, which is the major cause of death. Despite significant advances in diagnostic and therapeutic techniques, the survival rate of colorectal liver metastasis (CRLM) patients remains very low. CRLM, as a complex cascade reaction process involving multiple factors and procedures, has complex and diverse molecular mechanisms. In this review, we summarize the mechanisms/pathophysiology, diagnosis, treatment of CRLM. We also focus on an overview of the recent advances in understanding the molecular basis of CRLM with a special emphasis on tumor microenvironment and promise of newer targeted therapies for CRLM, further improving the prognosis of CRLM patients.

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References

Wu H, Huang S, Lu C, Tian S, Chen M . CircAPLP2 regulates the proliferation and metastasis of colorectal cancer by targeting miR-101-3p to activate the Notch signalling pathway. Am J Transl Res. 2020; 12(6):2554-2569. PMC: 7344090. View

Stiegelbauer V, Vychytilova-Faltejskova P, Karbiener M, Pehserl A, Reicher A, Resel M . miR-196b-5p Regulates Colorectal Cancer Cell Migration and Metastases through Interaction with HOXB7 and GALNT5. Clin Cancer Res. 2017; 23(17):5255-5266. DOI: 10.1158/1078-0432.CCR-17-0023. View

Donadon M, Hudspeth K, Cimino M, Di Tommaso L, Preti M, Tentorio P . Increased Infiltration of Natural Killer and T Cells in Colorectal Liver Metastases Improves Patient Overall Survival. J Gastrointest Surg. 2017; 21(8):1226-1236. DOI: 10.1007/s11605-017-3446-6. View

Chu P, Lin P, Wu H, Lin K, Wu C, Bekaii-Saab T . Mutant KRAS promotes liver metastasis of colorectal cancer, in part, by upregulating the MEK-Sp1-DNMT1-miR-137-YB-1-IGF-IR signaling pathway. Oncogene. 2018; 37(25):3440-3455. DOI: 10.1038/s41388-018-0222-3. View

Trusolino L, Comoglio P . Scatter-factor and semaphorin receptors: cell signalling for invasive growth. Nat Rev Cancer. 2002; 2(4):289-300. DOI: 10.1038/nrc779. View

Takahashi N, Haba A, Tabata M, Haruta Y, Tsai H, Seon B . Association of serum endoglin with metastasis in patients with colorectal, breast, and other solid tumors, and suppressive effect of chemotherapy on the serum endoglin. Clin Cancer Res. 2001; 7(3):524-32. View

Ding Y, Hao K, Li Z, Ma R, Zhou Y, Zhou Z . c-Fos separation from Lamin A/C by GDF15 promotes colon cancer invasion and metastasis in inflammatory microenvironment. J Cell Physiol. 2019; 235(5):4407-4421. DOI: 10.1002/jcp.29317. View

Jin L, Pan Y, Zhang J, Cao P . LncRNA HOTAIR recruits SNAIL to inhibit the transcription of HNF4α and promote the viability, migration, invasion and EMT of colorectal cancer. Transl Oncol. 2021; 14(4):101036. PMC: 7901038. DOI: 10.1016/j.tranon.2021.101036. View

Falcone A, Ricci S, Brunetti I, Pfanner E, Allegrini G, Barbara C . Phase III trial of infusional fluorouracil, leucovorin, oxaliplatin, and irinotecan (FOLFOXIRI) compared with infusional fluorouracil, leucovorin, and irinotecan (FOLFIRI) as first-line treatment for metastatic colorectal cancer: the Gruppo.... J Clin Oncol. 2007; 25(13):1670-6. DOI: 10.1200/JCO.2006.09.0928. View

10.

Yang H, Zhang H, Yang Y, Wang X, Deng T, Liu R . Hypoxia induced exosomal circRNA promotes metastasis of Colorectal Cancer via targeting GEF-H1/RhoA axis. Theranostics. 2020; 10(18):8211-8226. PMC: 7381736. DOI: 10.7150/thno.44419. View

11.

Okines A, Puerto O, Cunningham D, Chau I, Van Cutsem E, Saltz L . Surgery with curative-intent in patients treated with first-line chemotherapy plus bevacizumab for metastatic colorectal cancer First BEAT and the randomised phase-III NO16966 trial. Br J Cancer. 2009; 101(7):1033-8. PMC: 2768086. DOI: 10.1038/sj.bjc.6605259. View

12.

Wang L, Chen X, Sun X, Suo J . Long Noncoding RNA LINC00460 Facilitates Colorectal Cancer Progression by Negatively Regulating miR-613. Onco Targets Ther. 2020; 13:7555-7569. PMC: 7423399. DOI: 10.2147/OTT.S254489. View

13.

Zhou T, Wu L, Ma N, Tang F, Yu Z, Jiang Z . SOX9-activated FARSA-AS1 predetermines cell growth, stemness, and metastasis in colorectal cancer through upregulating FARSA and SOX9. Cell Death Dis. 2020; 11(12):1071. PMC: 7736271. DOI: 10.1038/s41419-020-03273-4. View

14.

Qiu Y, Yu H, Shi X, Xu K, Tang Q, Liang B . microRNA-497 inhibits invasion and metastasis of colorectal cancer cells by targeting vascular endothelial growth factor-A. Cell Prolif. 2016; 49(1):69-78. PMC: 6495881. DOI: 10.1111/cpr.12237. View

15.

Seubert B, Grunwald B, Kobuch J, Cui H, Schelter F, Schaten S . Tissue inhibitor of metalloproteinases (TIMP)-1 creates a premetastatic niche in the liver through SDF-1/CXCR4-dependent neutrophil recruitment in mice. Hepatology. 2014; 61(1):238-48. PMC: 4280301. DOI: 10.1002/hep.27378. View

16.

Larsen C . [Metastatic colonization of the liver by colorectal tumor cells is abolished by two micro-RNAs (miR-483-5p et miR-551a)]. Bull Cancer. 2015; 102(9):713-5. DOI: 10.1016/j.bulcan.2015.05.005. View

17.

Wang J, Lu T, Kung M, Yang Y, Yeh C, Tu Y . The Long Noncoding RNA LOC441461 (STX17-AS1) Modulates Colorectal Cancer Cell Growth and Motility. Cancers (Basel). 2020; 12(11). PMC: 7692211. DOI: 10.3390/cancers12113171. View

18.

Venook A, Niedzwiecki D, Lenz H, Innocenti F, Fruth B, Meyerhardt J . Effect of First-Line Chemotherapy Combined With Cetuximab or Bevacizumab on Overall Survival in Patients With KRAS Wild-Type Advanced or Metastatic Colorectal Cancer: A Randomized Clinical Trial. JAMA. 2017; 317(23):2392-2401. PMC: 5545896. DOI: 10.1001/jama.2017.7105. View

19.

Shoji Y, Takamura H, Ninomiya I, Fushida S, Tada Y, Yokota T . The Embryonic Stem Cell-Specific Transcription Factor ZFP57 Promotes Liver Metastasis of Colorectal Cancer. J Surg Res. 2019; 237:22-29. DOI: 10.1016/j.jss.2018.11.014. View

20.

Li Z, Liu J, Chen H, Zhang Y, Shi H, Huang L . Ferritin Light Chain (FTL) competes with long noncoding RNA Linc00467 for miR-133b binding site to regulate chemoresistance and metastasis of colorectal cancer. Carcinogenesis. 2019; 41(4):467-477. DOI: 10.1093/carcin/bgz181. View