Fig. 8: Hypothetical models of the PSPC1/PTK6 interaction modulating Wnt/β-catenin autocrine signaling and PSPC1-CT131 as a dual inhibitor of PSPC1 and PTK6 suppressing downstream oncogenic signaling. | Nature Communications

Fig. 8: Hypothetical models of the PSPC1/PTK6 interaction modulating Wnt/β-catenin autocrine signaling and PSPC1-CT131 as a dual inhibitor of PSPC1 and PTK6 suppressing downstream oncogenic signaling.

From: PSPC1-interchanged interactions with PTK6 and β-catenin synergize oncogenic subcellular translocations and tumor progression

Fig. 8: Hypothetical models of the PSPC1/PTK6 interaction modulating Wnt/β-catenin autocrine signaling and PSPC1-CT131 as a dual inhibitor of PSPC1 and PTK6 suppressing downstream oncogenic signaling.

a PTK6 suppressed PSPC1 oncogenic features by phosphorylation and interaction on Y523 of PSPC1 and was sequestered in the nucleus as a tumor suppressor. b PSPC1 upregulation or mutation of the PTK6 phosphorylation site PSPC1-Y523F augmented Wnt3a autocrine signaling to facilitate β-catenin nuclear and p-PTK6 cytoplasmic/membrane translocations to synergize the oncogenic signaling of both PSPC1 and PTK6, which facilitated EMT, stemness and metastasis. c Treatment of PSPC1-CT131 as a dual inhibitor of PSPC1 and PTK6 reduced the expression of both oncogenic PSPC1 and PTK6 to suppress HCC tumor progression. Overall, PSPC1-CT131, a dual inhibitor of PTK6 tyrosine kinase and PSPC1 pro-metastatic master activator, is a potent anticancer agent that prolongs the survival of mice in an HCC mouse model.

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