Inceptor correlates with markers of prostate cancer progression and modulates insulin/IGF1 signaling and cancer cell migration

• Published in: Molecular metabolism (Germany) Vol. 71; p. 101706
• Main Authors: Wissmiller, Katharina, Bilekova, Sara, Franko, Andras, Lutz, Stefan Z., Katsburg, Miriam, Gulde, Sebastian, Pellegata, Natalia S., Stenzl, Arnulf, Heni, Martin, Berti, Lucia, Häring, Hans-Ulrich, Lickert, Heiko
• Format: Journal Article
• Language: English
• Published: Germany Elsevier GmbH 01-05-2023; Elsevier
• Subjects: Androgen; Androgen Antagonists; Androgens; Cell Movement; Humans; IGF1R; Insulin; Insulin-Like Growth Factor I - metabolism; Insulins; Male; Original; Prostate - metabolism; Prostatic Neoplasms - metabolism; Signaling; Trafficking; Signaling; Androgen; Insulin; Trafficking; IGF1R
• ISSN: 2212-8778; 2212-8778
• DOI: 10.1016/j.molmet.2023.101706

The insulin/insulin-like growth factor 1 (IGF1) pathway is emerging as a crucial component of prostate cancer progression. Therefore, we investigated the role of the novel insulin/IGF1 signaling modulator inceptor in prostate cancer.
We analyzed the expression of inceptor in human samples of benign prostate epithelium and prostate cancer. Further, we performed signaling and functional assays using prostate cancer cell lines.
We found that inceptor was expressed in human benign and malignant prostate tissue and its expression positively correlated with various genes of interest, including genes involved in androgen signaling. In vitro, total levels of inceptor were increased upon androgen deprivation and correlated with high levels of androgen receptor in the nucleus. Inceptor overexpression was associated with increased cell migration, altered IGF1R trafficking and higher IGF1R activation.
Our in vitro results showed that inceptor expression was associated with androgen status, increased migration, and IGF1R signaling. In human samples, inceptor expression was significantly correlated with markers of prostate cancer progression. Taken together, these data provide a basis for investigation of inceptor in the context of prostate cancer.
•Inceptor levels correlate with carcinogenic markers in human prostate cancer.•Inceptor expression is associated with the androgen status of prostate cancer cells.•Overexpression of Inceptor modulates IGF1R signaling and trafficking.•Migration of a 3D spheroid model is induced by Inceptor.