Dataset Information

Integration of two in-depth proteomics approaches determines the high grade serous ovarian cancer-associated kallikrein-related peptidase 7 (KLK7) degradome

ABSTRACT: Kallikrein-related peptidase 7 (KLK7) is a serine peptidase that is over-produced in the most lethal form of ovarian cancer, called high grade serous ovarian cancer (HGSOC). To determine its underlying molecular mechanism of action, a comprehensive analysis of KLK7 degradome in the SKOV-3 cell-secreted proteins was performed using two complementary proteomic approaches, quantitative PROtein Topography and Migration Analysis Platform (qPROTOMAP) and Terminal Amine Isotopic Labelling of Substrates (TAILS).

INSTRUMENT(S): TripleTOF 5600

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Epithelial Cell, Cell Culture

DISEASE(S): Malignant Neoplasm Of Ovary

SUBMITTER: Lakmali Munasinghage Silva

LAB HEAD: Dist Prof Judith Ann Clements

PROVIDER: PXD003812 | Pride | 2019-02-15

REPOSITORIES: Pride

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Dataset's files

Source:

			Action	DRS
	qPROTOMAP_SKOV3_txt_repl1.zip	Other
	qPROTOMAP_SKOV3_txt_repl2.zip	Other
	qPROTOMAP_SKOV3_txt_repl3.zip	Other
	qPROTOMAP_SKOV3_wiff_repl1.zip	Other
	qPROTOMAP_SKOV3_wiff_repl2.zip	Other

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Publications

Integration of Two In-depth Quantitative Proteomics Approaches Determines the Kallikrein-related Peptidase 7 (KLK7) Degradome in Ovarian Cancer Cell Secretome.

Silva Lakmali Munasinghage LM Kryza Thomas T Stoll Thomas T Hoogland Christine C Dong Ying Y Stephens Carson Ryan CR Hastie Marcus Lachlan ML Magdolen Viktor V Kleifeld Oded O Gorman Jeffrey John JJ Clements Judith Ann JA

Molecular & cellular proteomics : MCP 20190131 5

Kallikrein-related peptidase 7 (KLK7) is a serine peptidase that is over expressed in ovarian cancer. <i>In vitro</i> functional analyses have suggested KLK7 to play a cancer progressive role, although monitoring of KLK7 expression has suggested a contradictory protective role for KLK7 in ovarian cancer patients. In order to help delineate its mechanism of action and thereby the functional roles, information on its substrate repertoire is crucial. Therefore, in this study a quantitative proteomi ...[more]

PMID: 30705123

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Project description:With the onset of resistance, ovarian cancer cells display almost unpredictable adaptive potential. This may derive from genetic ancestry of the tumor cells and can be additionally tailored by post translational protein modifications (PTMs). The latter are profoundly shaped by the physical and chemical cues of the cancer microenvironment which, for ovarian cancer, is primarily the abdominal cavity. In this study, we took advantage of high-end proteome and phosphoproteome analyses combined with multiparametric morphometric profiling for the description of the proteome signatures of high-grade serous carcinomas (OVCAR-3) and non-serous carcinomas (SKOV-3) ovarian cancer cells. For the functional experiments, we applied two different protocols, representing typical stimuli of the peritoneal cavity and of the growing tumor mass: on the one side hypoxia (oxygen 1%) which develops within the tumor mass or is experienced during migration/extravasation in non-vascularized tissues. For comparison, fluid shear stress (2.8 dyn/cm2, orbital shaker method) which characterizes the tumor surface in peritoneal cavity or metastases spread in the bloodstream. After 3 hours incubation, treatment groups were clearly distinguishable by PCA analysis. Whereas basal proteome profile of SKOV-3 and OVCAR-3 cells appeared almost unchanged, phosphoproteome analysis revealed multiple regulations. These affected primarily cellular structure and proliferative potential and consolidated after 24h treatment. Albeit maintaining their individuality, hypoxia modified cell metabolism and morphology of both OVCAR-3 and SKOV-3: upon oxygen reduction cell size increased in concerted regulation of pathways related to Rho-GTPases and/or cytoskeletal elements (proteome and phosphoproteome). Also shear stress stimulation sharpened the response profile of SKOV-3 and OVCAR-3: this retraced their pathophysiological behavior and actively modified structural proteins as well as metabolism (e.g. delta(14)-sterol reductase, Kinesin-like proteins (KIF-22/20A) and Actin-related protein 2/3 complex). In conclusion, we characterized a biochemical and structural fingerprinting describing the adaptive potential of ovarian cancer cells to physical/chemical stressors typical for the abdominal cavity.