TITLE:
Cell-type specific and non-redundant anti-proliferative effects of shRNA-mediated Galpha12- and Galpha13 knockdown in lung cancer cell lines
AUTHORS:
Thomas R. H. Büch, Marius Grzelinski, Olaf Pinkenburg, Thomas Gudermann, Achim Aigner
KEYWORDS:
KEYWORDS Galpha12; Galpha13; G12/13; Lung Cancer; SCLC; NSCLC; Gene Knockdown
JOURNAL NAME:
Advances in Bioscience and Biotechnology,
Vol.5 No.1,
January
23,
2014
ABSTRACT: In small cell lung cancer cells, various autocrine
stimuli lead to the parallel activation of Gq/11 and G12/13 proteins. The contribution of the Gq/11-PLC-β cascade to the mitogenic
effects in SCLC cells is well established, but the relevance of G12/13 signaling is less explored. While in prostate and breast cancer, G12/13 activation has been shown previously to promote invasiveness without being
involved in cellular proliferation, previous data from our group indicate anti-proliferative effects of G12/13 knockdown in small cell lung cancer
(SCLC) cells. To further investigate the role of G12/13-dependent
signaling in lung tumor cells, we employed shRNA-mediated targeting of Gα12,
Gα13,
or both, in SCLC and NSCLC cell lines. Lentiviral expression of shRNAs resulted
in specific Gα12 and Gα13 knockdown. Of note, upon single knockdown of one family member, no counter-upregulation
of the other one was observed. Interestingly, inhibition of proliferation was
cell line dependent. In cell lines where knock-down led to antiproliferation, single
knockdown of either Gα12 or Gα13 was sufficient to impair proliferation and double knockdown of Gα12 and Gα13 tended not to further increase anti-proliferative
effects. Likewise, when single knockdown was insufficient for an
inhibition of proliferation, no effects were observed in double knockdowns.
Taken together, these findings indicate that both Gα12 and Gα13 affect cellular proliferation individually and interference with one family
member is sufficient for anti-tumor effects.