METCAM/MUC18, a cell adhesion molecule in the Ig-like gene superfamily, plays an important role in promoting tumor angiogenesis in many tumors and in the progression of epithelial tumors.However, the role of METCAM/MUC18 in the progression of breast carcinoma has been controversial: the results from two groups appeared to support that METCAM/MUC 18 serves as a tumor suppressor, and on the contrary, the results of two other groups support that METCAM/MUC18 plays a positive role in the progression of the cancer.To resolve the controversy, we have reinvestigated the role of METCAM/MUC 18 in the progression of four human breast cancer cell lines: MCF7 and SKBR-3 (from epithelial subtype) and MDA-MB-231 and MDA-MB-468 (from basal-like subtype).We have found that METCAM/MUC 18 expression increased in vitro motility and invasiveness and tumorigenesis (anchorage-independent growth and 3D growth in matrigel) of these four breast cancer cell lines and also in vivo tumorigenesis of MCF7 and SK-BR-3 cells.We have also shown that METCAM/MUC 18 increased tumorigenesis of breast cancer cells by increasing anti-apoptosis, aerobic glycolysis, and angiogenesis, but had no effect on apoptosis, similar to that in melanoma and prostate cancer cells.Taken together, we have provided in vitro and in vivo evidence to favor the notion that METCAM/MUC 18 expression promotes the progression of breast cancer cells.