Cross talk between apoptosis and invasion signaling in cancer cells through caspase-3 activation.
In solid tumors, cancer cells are exposed to various microenvironmental stresses such as hypoxia, nutritional depletion, and low pH. Cancer cells adapt to these stresses and circumvent cell death. When the antiapoptotic signals overcome the stress, cancer cells might acquire physiologic functions, such as invasiveness, instead of cell death. Here, we report that tumor cells acquire an invasive capacity from apoptotic signals through caspase activation. We treated rat ascites hepatoma MM1 cells with an apoptosis-inducing drug, etoposide, or hypoxia, and assessed the invasion capacity with an in vitro bioassay. Although MM1 cells hardly showed invasiveness in serum-free medium, under stress conditions, invasive capacity accompanied with morphologic change was induced with caspase-3 activation. Such stress-induced invasion as well as morphologic change was suppressed by blocking caspase-3 activity with caspase inhibitors or by RNA interference of caspase-3. In contrast, lysophosphatidic acid-induced invasiveness was not affected by caspase-3 inhibition. These results suggest that caspase-3 activation contributes to the stress-induced invasive capacity of these cancer cells.
Mukai
Mutsuko
M
Departments of Biochemistry and Gastrointestinal Oncology, Osaka Medical Center for Cancer and Cardiovascular Diseases, Nakamichi, Higashinari-ku, Osaka, Japan.
Kusama
Toshiyuki
T
Hamanaka
Yukou
Y
Koga
Takumi
T
Endo
Hiroko
H
Tatsuta
Masaharu
M
Inoue
Masahiro
M
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D001943:Breast Neoplasms / Q000201:enzymology* / Q000473:pathology; D053148:Caspase 3; D061945:Caspase Inhibitors; D020169:Caspases / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D004789:Enzyme Activation; D005047:Etoposide / Q000494:pharmacology; D020868:Gene Silencing; D006801:Humans; D008114:Liver Neoplasms, Experimental / Q000201:enzymology* / Q000473:pathology; D009361:Neoplasm Invasiveness; D051381:Rats; D015398:Signal Transduction
D061945:Caspase Inhibitors; D005047:Etoposide; C505407:CASP3 protein, human; C505410:Casp3 protein, rat; D053148:Caspase 3; D020169:Caspases