Syncytin 1, CD9, and CD47 regulating cell fusion to form PGCCs associated with cAMP/PKA and JNK signaling pathway

We have previously reported the formation of polyploid giant cancer cells (PGCCs) through endoreduplication or cell fusion after cobalt chloride (CoCl₂ ) induction. Cell fusion plays an important role in development and disease. However, the underlying molecular mechanism concerning cell fusion in PGCCs formation and clinicopathological significances remains unclear.

We treat HCT116 and LoVo cell with CoCl₂ and observed the cell fusion via fluorescent markers of different colors. Western blot and immunocytochemical staining were used to compare the expression and subcellular location of the fusion-related proteins syncytin 1, CD9, and CD47 along with PKA RIα, JNK1, and c-Jun between PGCCs and control cells from the HCT116 and LoVo cell lines. Moreover, 173 cases of colorectal tumor tissue samples were analyzed, including 47 cases of well-differentiated primary colorectal cancer (group I) and 5 cases of corresponding metastatic tumors (group II), 38 cases of moderately differentiated primary colorectal cancer (group III) and 14 cases of corresponding metastatic tumors (group IV), and 42 cases of poorly differentiated primary colorectal cancer (group V) and 27 cases of corresponding metastatic tumors (group VI).

The expression of syncytin 1, CD9, and CD47 is higher in PGCCs than in control cells and they are located in the cytoplasm. The expression of PKA RIα and JNK1 decreased, and that of c-Jun increased in PGCCs. The syncytin 1 expression was significantly different between groups I and II (P = 0.000), groups III and IV (P = 0.000), groups V and VI (P = 0.029), groups I and III (P = 0.001), groups III and V (P = 0.000), and groups I, III, and V (P = 0.000).

These data indicate that the cell fusion-related proteins syncytin 1, CD9, and CD47 may be involved in PGCC formation, and that cAMP/PKA and JNK signaling is likely to promote PGCC formation via the regulation of cell fusion processes.