Metastatic suppression by DOC2B is mediated by inhibition of epithelial-mesenchymal transition and induction of senescence

Bhat, Samatha and Adiga, Divya and Shukla, Vaibhav and Guruprasad, KP and Kabekkodu, Shama Prasada and Satyamoorthy, K (2022) Metastatic suppression by DOC2B is mediated by inhibition of epithelial-mesenchymal transition and induction of senescence. Cell Biology and Toxicology, 38 (9). pp. 237-258. ISSN 0742-2091

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Senescence induction and epithelial-mesenchymal transition (EMT) events are the opposite sides of the spectrum of cancer phenotypes. The key molecules involved in these processes may get influenced or altered by genetic and epigenetic changes during tumor progression. Double C2-like domain beta (DOC2B), an intracellular vesicle trafficking protein of the double C2 protein family, plays a critical role in exocytosis, neurotransmitter release, and intracellular vesicle trafficking. DOC2B is repressed by DNA promoter hypermethylation and functions as a tumor growth regulator in cervical cancer. To date, the molecular mechanisms of DOC2B in cervical cancer progression and metastasis is elusive. Herein, the biological functions and molecular mechanisms regulated by DOC2B and its impact on senescence and EMT are described. DOC2B inhibition promotes proliferation, growth, and migration by relieving G0/G1-S arrest, actin remodeling, and anoikis resistance in Cal27 cells. It enhanced tumor growth and liver metastasis in nude mice with the concomitant increase in metastasis-associated CD55 and CD61 expression. Inhibition of EMT and promotion of senescence by DOC2B is a calcium-dependent process and accompanied by calcium-mediated interaction between DOC2B and CDH1. In addition, we have identified several EMT and senescence regulators as targets of DOC2B. We show that DOC2B may act as a metastatic suppressor by inhibiting EMT through induction of senescence via DOC2B-calcium-EMT-senescence axis.

Item Type: Article
Uncontrolled Keywords: DOC2B; Epithelial-mesenchymal transition; Metastasis; Senescence; Calcium; Cervical cancer; Abbreviations; BAPTA-AM-1,2-bis(oaminophenoxy) ethane-N, N,N′, N′- tetraacetic acid ester; SA-βga-lSenescence-associated β galactosidase; SASP-Senescence-associated secretory phenotype; EMT-Epithelial to mesenchymal transition.
Subjects: Life Sciences > MLSC Manipal
Depositing User: KMC Library
Date Deposited: 25 Jul 2022 08:39
Last Modified: 25 Jul 2022 08:39

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