Colourectal cancer (CRC) is one of the most common gut tumours on the planet, the fourth leading cause of death and second leading cause of cancer death in the world. While surgery and resection helped the outcome of early-stage CRC, the outcome is bad for the majority of patients with CRC due to recurrence and dissemination. DNA and protein profiling of CRC molecule is now increasingly used to discover prognostic biomarkers and design novel therapies.
Lung adenocarcinoma is one of the most common lung cancers on the planet and its survival has not really improved, so we have good targets. TCN1: an anti-caking B12 protein which maintains the cobalin. TCN1 levels are high in the tumour tissues, and cancer aggressiveness and outcome are related, based on current research and bioinformatics analysis. But how it might act on lung adenocarcinoma (LUAD) is unknown.
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Transcobalamin 1 (TCN1)
The cobalamine-binding protein (TBP) B12 (cobalamin) transcobalamin I (TCN1) carries cobalamin from the stomach into the intestine. Transcobalamin 1 (TCN1) or vitamin B12 (cobalamin) R binding protein: This is one of three vitamin B12 transporters that can be detected in blood and body fluids. TCN1 transports vitamin B12 from the gut to the duodenum and is released by enzymes that link to factors intrinsic. TCN1 is over-proliferated in malignant tumors (hepatocellular carcinoma, leukemia, breast cancer, lung cancer, gastric cancer). TCN1 is an important oncogene. Next-generation sequencing demonstrated that TCN1 is one of those genes overexpressed in CRC. Several researchers reported that the levels of TCN1 in CRC correlate strongly with malignant biological behavior.
Transcobalamin 1 (TCN1) Deficiency Regulates ITGB4 Pathway
TCN1 knockdown suppresses CRC cell proliferation and invasion, and apoptotic effect; overexpression of TCN1 causes the reverse. Further, HCT116 cells knocked down in TCN1 could not form metastatic foci in the peritoneum after intravenous injection. In a molecule mechanism study, we identified TCN1 binding to integrin subunit 4 (ITGB4) and positively influencing ITGB4 expression. TCN1 knockdown increases ITGB4 degradation and ITGB4 and filamin A instability Downregulation of ITGB4 at the protein level results in dissociation of the ITGB4/plectin complex and cytoskeletal disruption.
Expression of Transcobalamin 1 (TCN1) in Various Tumors
TCN1 was also hyperexpressed versus control tissue in COAD, bladder urothelial carcinoma (BLCA), cholangiocarcinoma (CHOL), renal papillary cell carcinoma (KIRP), uterine corpus endometrial carcinoma (UCEC), lung squamous cell carcinoma (LUSC) and lung adenocarcinoma (LUAD). Lymphoid tumours expressed far less in diffuse large B-cell lymphoma (DLBC), breast invasive carcinoma (BRCA), liver cancer (LIHC), testicular germ cell tumor (TDCT), acute myeloid leukemia (LAML) and head and neck squamous cell carcinoma (HNSC) than in healthy control tissue.
Transcobalamin 1 (TCN1) In Overexpression in Colorectal Cancer (CRC) Tissues
TCN1 is abundantly expressed in most colon cancer tissue on the protein and mRNA levels, but far less so in normal colon mucosal tissues adjacent to it. TCN1 mRNA is higher than usual in non-cancerous tissues (relatively). The cytoplasm is the part of the body where TCN1 is most immunoreactive. Expression of TCN1 in the colon cancer cells is far greater than in nearby normal tissue. Positive for TCN1 in lung metastatic tissue exceeds positive for primary colon cancer tissue.
Fig.1 Transcobalamin 1 (TCN1) and integrin subunit β4 (ITGB4) are highly expressed in colorectal cancer (CRC) clinical tissues (Zhu, X., et al. 2022).
TCN1 May Be a Prognostic Indicator
TCN1 (in the vitamin B12 binding proteins family) is a 60-70 kDa protein that is a granulocyte lineage protein. TCN1 is increased in the cytoplasm of tumour tissue. TCN1 is hyperactive in a few tumour types that promote the growth and spread of the tumour: colon cancer, hypopharyngeal squamous cell carcinoma, breast cancer, gastric cancer. TCN1 over-expression in the tumor cells causes tumourigenesis and distorted biology. TCN1 might be a new colorectal cancer oncogene. TCN1 could be used as a prognostic and diagnostic biomarker, and to develop therapeutic and prognostic biomarkers for LUAD. Overexpression of TCN1 is a bad news biomarker for neoadjuvant chemotherapy resistance in colon cancer.
Transcobalamin 1 (TCN1) Serve as a Biomarker for Chemotherapy Resistance
TCN1 is a cytoplasmic vitamin B12 binding protein that acts as a transport, metabolism and homeostatic regulator of vitamin B12 along with TCN2 and intrinsic factor. The oncogene TCN1 is overexpressed in CRC. TCN1 knockdown prevents CRC cell proliferation and invasion and kills cells; TCN1 overexpression leads to the opposite result. Moreover, HCT116 cells knocked down for TCN1 could not create metastatic foci in the peritoneum when they were injected with intravenous fluid. We have determined through molecular mechanism analysis that TCN1 crosses over to integrin subunit 4 (ITGB4) and regulates ITGB4 expression in a positive manner. TCN1 knockdown increases the turnover of ITGB4 and renders ITGB4 and filamin A more unstable. Downregulation of ITGB4 on the protein level dissociates the ITGB4/plectin complex and damages the cytoskeleton. TCN1 is overexpressed in colon cancer and has advanced pathology. TCN1 could be used as a prognostic factor and a biomarker for chemotherapy resistance.
References
- Zhu, X., et al. TCN1 deficiency inhibits the Malignancy of colorectal cancer cells by regulating the ITGB4 pathway. Gut and Liver. 2022, 17(3): 412.
- Liu, G., et al. High expression of TCN1 is a negative prognostic biomarker and can predict neoadjuvant chemosensitivity of colon cancer. Scientific reports. 2020, 10(1): 11951.
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