Hp95 promotes anoikis and inhibits tumorigenicity of HeLa cells.
p95 is a putative signal transduction protein of approximately 95 kDa that contains multiple tyrosine residues that are conserved from yeast to human, a Src phosphorylation consensus sequence and a proline-rich C-terminus that binds SH3-domains. Previous studies have established that mammalian p95 is physically associated with proteins that regulate apoptotic induction and cell transformation; however, it is unclear whether p95 is a positive or negative regulator in these processes. Moreover, a p95 partner protein has been localized at both focal adhesions and actin-cytoskeletons in rat astrocytes. However, there is no evidence that mammalian p95 has roles in regulating cell adhesion or morphology. In this study, we examined the effects of p95 on the anchorage-independent growth and tumorigenicity of malignant HeLa cells, and on the growth and morphology of non-transformed NIH3T3 cells. In HeLa cells, p95 overexpression promoted detachment-induced apoptosis (anoikis), inhibited detachment of viable cells from substratum and reduced tumorigenicity. In NIH3T3 cells, p95 overexpression promoted flat cell morphology and slowed cell proliferation, whereas p95 downregulation had opposite effects. These findings indicate that the mammalian p95 is a positive regulator in apoptotic signaling and a negative regulator in cell transformation. They also suggest that p95 has roles in regulating cell adhesion and morphology.
D016475:3T3 Cells; D000818:Animals; D023102:Anoikis; D017209:Apoptosis; D002135:Calcium-Binding Proteins; D002352:Carrier Proteins; D002448:Cell Adhesion; D018797:Cell Cycle Proteins / Q000502:physiology*; D002455:Cell Division; D056827:Endosomal Sorting Complexes Required for Transport; D016193:G1 Phase; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009374:Neoplasms, Experimental / Q000517:prevention & control*; D010750:Phosphoproteins / Q000502:physiology*; D015398:Signal Transduction
D002135:Calcium-Binding Proteins; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D056827:Endosomal Sorting Complexes Required for Transport; C117020:PDCD6IP protein, human; D010750:Phosphoproteins