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Simple Summary: Different connexins play diverse roles in cancers, either tumor-suppressing or tumor-promoting. In lung cancer, Cx43 serves as a tumor suppressor at the early stage, but it can also be a tumor-promotor at an advanced stage and during metastasis. Moreover, other connexins, including Cx26, Cx31.1, and Cx32, can be tumor suppressors. In contrast, Cx30.3 can be a tumor-promotor. The roles of different connexins in different cancers have also been established. Cx43 acts as a tumor suppressor in colorectal cancer, breast cancer, and glioma, whereas Cx32 can be a suppressor in liver tumors and hepatocarcinogenesis. Cx26 can be a tumor suppressor in mammary tumors; in contrast, it can be a tumor-promotor in melanoma. Existing drugs/molecules targeting the cAMP/PKA/connexin axis act to regulate channel opening/closing. Mimic peptides, such as Gap19, Gap26, and Gap 27 block hemichannels, mimetic peptides, and CT9/CT10 and promote hemichannel opening and also hemichannel closing. Connexin-containing gap junctions mediate the direct exchange of small molecules between cells, thus promoting cell–cell communication. Connexins (Cxs) have been widely studied as key tumor-suppressors. However, certain Cx subtypes, such as Cx43 and Cx26, are overexpressed in metastatic tumor lesions. Cyclic adenosine monophosphate (cAMP) signaling regulates Cx expression and function via transcriptional control and phosphorylation. cAMP also passes through gap junction channels between adjacent cells, regulating cell cycle progression, particularly in cancer cell populations. Low levels of cAMP are sufficient to activate key effectors. The present review evaluates the mechanisms underlying Cx regulation by cAMP signaling and the role of gap junctions in cancer progression and metastasis. A deeper understanding of these processes might facilitate the development of novel anticancer drugs. [ABSTRACT FROM AUTHOR]

Two physiological changes of Spodoptera litura parasitized by Microplitis bicoloratus are hemocyte-apoptosis and retarded immature development. β-Chain of F o F 1 -ATPase was found from a S. litura transcriptome. It belongs to a conserved P-loop NTPase superfamily, descending from a common ancestor of Lepidopteran clade. However, the characterization of β-chain of ATPase in apoptotic cells and its involvement in development remain unknown. Here, the ectopic expression and endogenous F o F 1 -ATPase β-chain occurred on S. litura cell membrane: in vivo, at the late stage of apoptotic hemocyte, endogenous F o F 1 -ATPase β-chain was stably expressed during M. bicoloratus larva development from 4 to 7 days post-parasitization; in vitro, at an early stage of pre-apoptotic Spli221 cells by infecting with M. bicoloratus bracovirus particles, the proteins were speedily recover expression. Furthermore, endogenous F o F 1 -ATPase β-chain was localized on the apoptotic cell membrane. RNA interference (RNAi) of F o F 1 -ATPase β-chain led to significantly decreased head capsule width. This suggested that F o F 1 -ATPase β-chain positively regulated the development of S. litura. The RNAi effect on the head capsule width was enhanced with parasitism. Our research found that F o F 1 -ATPase β-chain was expressed and localized on the cell membrane in the apoptotic cells, and involved in the development of S. litura., (© 2017 Wiley Periodicals, Inc.)

Microplitis bicoloratus is a braconid endoparasitic wasp associated with the polydnavirus named Microplitis bicoloratus bracovirus (MbBV). Parasitism of Spodoptera litura larvae leads to an impaired cellular immune response and to the disappearance of the 42 kDa actin in host hemocytes. In this work, we investigated if the absence of actin in blood cells was related to MbBV infection. An MbBV gene similar to egf-like genes identified in another bracovirus was partially cloned and named Mbcrp1. The full-length gene, named Mbcrp, is transcribed throughout the course of parasitism in host hemocytes and the 30 kDa MbCRP protein was detected in hemocytes 6-7 d post-parasitization. The Mbcrp1 gene contains the cysteine-rich trypsin inhibitor-like (TIL) domain coding sequence and the expression of recombinant MbCRP1 inhibited the expression of the 42 kDa actin in Hi5 cells. The 34.1 kDa MbCRP1-green fluorescent protein fusion protein locate specifically in the cytoplasm. These results suggest that expression of MbCRP in lepidopteran insect cells is related to the disruption of the actin cytoskeleton.