Table 2.
Cancer Type | Evidence for CBS Up-regulation | Effect of CBS Silencing | Reference |
---|---|---|---|
Biliary tract carcinoma | CBS cRNA hybridization levels measured on oligonucleotide microarray are higher in gallbladder carcinoma, intrahepatic cholangiocarcinoma, distal bile duct carcinomas, EGI-1, TFK-1, HUH28, HUCCT-1, SNU 245, SNU 308, SNU 1079, GB-H3, and GB-D1 cells than in normal extrahepatic biliary and gallbladder epithelial scrapings | Not tested | [287] |
Breast cancer | • CBS mRNA levels detected by RT-qPCR and protein levels detected by immunoblotting are both higher in Hs 578T, MCF-7, and MDA-MB-468 cells than in HMEC and MCF-10A cells • CBS protein levels detected by immunohistochemistry are increased with the disease progression on tissue microarray with 60 human breast cancer tissue, and compared to the controls human breast epithelial tissue • CBS protein levels detected by immunoblotting are higher in doxorubicin-resistant MCF-7 cells that in normal MCF-7 cells |
• Silencing of CBS in MCF-7 and MDA-MB-468 cells reduces cell viability in the presence of GOx, DOX or activated macrophages • Silencing of CBS in MCF-7 cells reduces xenograft growth in female Balb/c nude mice • Silencing of CBS in MCF-7 and MDA-MB-468 cells causes dilation of the ER and increases cytosolic calcium concentrations • Silencing of CBS in MCF-7 and MDA-MB-468 cells decreases cristae formation and increases vacuole formation in mitochondria, increases MPTP opening, and decreases mitochondrial reserve capacity |
[82,289,294] |
Colon cancer | • CBS protein levels detected by immunoblotting are higher in human colorectal tumor tissues compared to respective normal mucosa tissues • CBS protein levels detected by immunoblotting are higher in LoVo, HCT116, and HT29 cells compared to NCM356 cells • CBS protein levels detected by immunoblotting are higher in premalignant polyps compared to normal mucosa tissues • CBS protein levels detected by immunohistochemistry are increased in hyperplastic polyps compared to normal crypt cells • CBS protein levels detected by immunohistochemistry on tissue microarray are increased in 40 human colon cancer tissues compared to paired adjacent tissues over 52 colorectal cancer cases • CBS protein levels are increased in the colon cancer cell derived circulating tumor cell population CTC-MCC-41 • The development of multi-drug resistance is associated with an up-regulation of CBS protein in HCT116 cells |
Silencing of CBS in HCT116 cells decreases cell proliferation and cellular bioenergetics in vitro and attenuates HCT116 xenograft growth and vascularization in female Balb/c nude mice | [88,290,296,300,302,303,308,309,310,313,315,318] |
Glioma | CBS mRNA levels detected by PCR and protein levels detected by immunoblotting are both higher in U-87 MG cells than in SHSY5Y cells | • Not tested | [301] |
Liver cancer | • CBS protein levels detected by immunoblotting are higher in HepG2 cells and SMMC-7721 than in HL-7702 cells a • In HepG2 cells stress conditions (e.g., oxidative stress, chemotherapeutics, irradiation) induces cancer cell stemness and multi-drug resistance and this is associated with up-regulation of CBS protein |
• Silencing of CBS in SMMC-7721 decreases cell viability and proliferation, increases ROS levels and apoptosis | [291,293,297,312,314] |
Lung cancer | • CBS mRNA levels detected by RT-qPCR and CBS protein levels detected by immunoblotting are higher in human primary tumor tissues compared to matched human normal tissues • CBS protein levels detected by immunoblotting are higher in human lung adenocarcinoma tumors than in normal adjacent tissues • CBS protein levels detected by immunoblotting are higher in A549, H522, and H1944 cells compared to BEAS 2B cells |
• Down-regulation of CBS by rpL3 enhances Calu-6 cells apoptosis and reduces cell migration and invasion • Transient CBS depletion represses mtDNA repair and increases CPT-induced necrosis in A549 cells |
[298,299,319] |
Multiple myeloma | • cRNA hybridization levels for CBS, measured on oligonucleotide microarray, are higher in human malignant plasma cells from patients with multiple myeloma than in normal plasma cells • mRNA levels detected by RT-qPCR are higher in HMCL than in PPCL |
Not tested | [286] |
Ovarian cancer | • Human ovarian tumor tissues exhibited moderate-strong CBS protein expression detected by immunohistochemistry on tissue microarray • CBS mRNA levels detected by RT-qPCR and protein levels detected by immunoblotting are both higher in OV167, OV202, SKOV3, and A2780 cells than in OSE cells • CBS protein levels detected by immunoblotting are higher in OV90, CP20, OVSAHO, Kuramochi, and TykNu and cisplatin-resistant TykNu cells than in OSE, FTE188 and HOSE cells • The ferroptosis inducer small-molecule erastin induced an up-regulation of CBS protein and yielded an erastin-resistant version of ovarian cancer cell lines SKOV3 and OVCA429. |
• Silencing of CBS in OV202, SKOV3, A2780, and cisplatin-resistant A2780 decreases total cellular glutathione level and cell proliferation • Silencing of CBS in A2780 cells increases cellular and mitochondrial ROS levels, down-regulates NF-κB, decreases cellular bioenergetics, and sensitizes to cisplatin • Silencing of CBS in cisplatin-resistant A2780 reduces xenograft growth and vascularization, and nodules formation in female nude mice, enhances sensitivity to cisplatin, and decreases MFN2 expression • Silencing of CBS in CP20 and OV90 decreases cell proliferation, mitochondrial membrane potential, and network by promoting mitochondrial fission, cellular bioenergetics and promotes MFN2 degradation • In the erastin-resistant version of ovarian cancer cell lines SKOV3 and OVCA429, CBS silencing induces cell death via induction of ferroptosis |
[89,292,306,307,317] |
Prostate cancer | • CBS protein levels detected by immunoblotting are higher in BPH-1, LNCaP, and DU145 cells than in RWPE-1 and WPMY-1 cells • CBS protein levels measured by immunofluorescence are higher in LNCaP cells than in RWPE-1 cells |
Not tested | [83] |
Renal carcinoma | • CBS protein levels detected by immunohistochemistry are increased with the disease progression on tissue microarray, and in 53 renal urothelial carcinomas and 9 renal clear cell carcinomas at Fuhrman grade IV compared to 11 benign renal cortex tissues • cRNA hybridization levels of CBS, measured on oligonucleotide microarray are higher in 2 angiomyolipoma and 3 papillary carcinoma tissues compared to respective unaffected part of kidney tissues |
Not tested | [304,305] |
Bladder cancer | CBS protein levels were detected in bladder tissue specimens (gallbladder squamous cell/adenosquamous carcinomas and adenocarcinomas) and in the bladder carcinoma cell lines 5637, EJ, and UM-UC-3 | Not tested | [311] |
Thyroid cancer | Increased CBS protein levels were detected in thyroid carcinomas compared to benign thyroid tissue (but not in thyroid follicular adenomas or oncocytomas) | Not tested | [73] |