“In humans, the GIP gene functions as an oncogene in ovarian tumors.”

Recent studies have shown that the gip2 and gep oncogenes defined by the α-subunits of Gi2 and G12 family of G proteins, namely Gαi2 and Gα12/13, stimulate oncogenic signaling pathways in cancer cells including those derived from ovarian cancer. Due to intrinsic potential of activating tumorigenic pathways, the activated forms of Gαi2 and Gα12/13 subunits are referred to as gip2 and gep oncogenes. Thus, our studies establish for the first time that Gα12/13, the putative gep oncogenes, are the determinant α-subunits involved in ovarian cancer growth in vivo.

An increasing body of evidence suggests that endocrine G protein-coupled receptors (GPCRs) are involved in the progression and metastasis of ovarian neoplasms. FSHR acts as an oncogene in ovarian cancer. Overexpression of follicle-stimulating hormone receptor facilitates the development of ovarian epithelial cancer.

Increased expression of GNAi2, which encodes the α-subunit of G-protein i2, has been correlated with the late-stage progression of ovarian cancer. GNAi2, also referred to as the proto-oncogene gip2, transduces signals from lysophosphatidic acid (LPA)-activated LPA-receptors to oncogenic cellular responses in ovarian cancer cells. Functional annotation of the transcriptome indicated the hitherto unknown role of gip2 in stimulating the expression of oncogenic/growth-promoting genes such as KDR/VEGFR2, CCL20, and VIP.

GNAI2 guanine nucleotide binding protein G(i) subunit alpha 2 [Homo sapiens (human)]. G protein alpha subunit that functions as a heterotrimeric G protein. No direct mention of oncogenic role in ovarian cancer; associated with signaling pathways but not classified as an oncogene in primary records.

Concerning ovarian cancer, current evidence suggests that GLP-1RAs are not associated with an increased risk of ovarian cancer. Preclinical studies have demonstrated that Ex-4 exhibits anti-tumor effects in human ovarian cancer cell lines SKOV-3 and CAOV-3 by activating the GLP-1R, and Ex-4 has been shown to inhibit the growth of ovarian cancer cells and induce apoptosis.

Evidence from experimental models shows that glucose-dependent insulinotropic peptide (GIP) agonists, such as tirzepatide, have been shown to promote tumor proliferation in a dose-sensitive manner, particularly in colorectal cancer cell lines. GIP signaling may pose oncologic concerns, and tirzepatide may increase the synthesis of insulin, IGF-1, IGF-2, and their binding proteins—factors linked to elevated cancer risk.

While some studies suggest GNAI2 (gip2) involvement in oncogenic signaling, comprehensive analysis in ovarian cancer cohorts shows no consistent overexpression or prognostic correlation with poor survival; instead, certain mutations may act tumor-suppressively. No evidence supports classification as an oncogene specific to ovarian tumors.

Use of GLP-1RA was associated with substantially improved overall survival in women with ovarian cancer. This finding suggests that inhibition of GLP-1 signaling pathways may have therapeutic benefit, implying that related incretin pathways (including GIP signaling) warrant investigation in ovarian cancer biology.

GPR176 overexpression promoted the proliferation, anti-apoptosis, anti-pyroptosis, migration and invasion of ovarian cancer cells.

Activated mutants of Galpha(i2) (gip2 oncogene) transform NIH 3T3 cells and induce metastasis in nude mice. Expression of gip2 is elevated in metastatic hamster pancreas tumors. These findings suggest that gip2 functions as a metastasis-associated oncogene.

CEMIP expression level in ovarian cancer tissues was higher than that in normal ovaries. Silencing of CEMIP in ovarian cancer cell lines significantly decreased cell proliferation, cell migration and invasion capacity, while the proportion of apoptotic cells was increased. These findings establish that elevated expression of migration-inducing proteins can function as oncogenic drivers in ovarian cancer through PI3K/AKT pathway activation.

OIP5 was highly expressed in ovarian cancer and downregulation of OIP5 inhibited the proliferation, migration and invasion of ovarian cancer cells. OIP5 knockdown increased apoptosis and arrested cell cycle progression at the G1 phase. The study demonstrates that upregulation of OIP5 promotes ovarian cancer progression through AKT activation and mTORC2 signaling, providing evidence that genes promoting cell proliferation and survival can function as oncogenes in ovarian tumors.

GIP receptors interact with estrogens in the hypothalamic regulation of food intake in mice, and their blockade may carry promising potential for therapeutic intervention. This study indicates that GIP receptor signaling has biological activity in mammalian systems and may be a target for therapeutic modulation.

The GIP gene encodes glucose-dependent insulinotropic polypeptide, an incretin hormone involved in glucose homeostasis and insulin secretion. The gene is primarily expressed in intestinal K cells and has established roles in metabolic regulation. Current literature does not identify GIP as a characterized oncogene in ovarian cancer or other malignancies.

Clinical trial testing the safety of glucose-dependent insulinotropic peptide (GIP)/GIP Analog on people with Type 2 Diabetes, focusing on metabolic and endocrine effects rather than oncogenic properties.

Expression of GIP in cancer tissue. The cancer tissue page shows antibody staining of the protein in 20 different cancers. Kaplan-Meier plots for all cancers where high expression of this gene has significant (p<0.001) association with patient survival are shown in this summary. Whether the prognosis is favorable or unfavorable is indicated in brackets.

Here we elucidate GNAI2 message alterations in ovarian cancer (OvCa). GNAI2 is a heterotrimeric G protein which couples cell surface hormone receptors to intracellular signaling proteins.

A large study suggests that widely used diabetes and weight-loss drugs may also help women with ovarian cancer live longer, indicating a potential protective or therapeutic association rather than an oncogenic one.

Endometriosis‑associated ovarian cancers demonstrate substantial morphological and genetic diversity. The transcription factor, hepatocyte nuclear factor-4α (HNF4α), has been implicated in endometriosis-associated ovarian cancers.

The oncogene ALC1 can promote cisplatin resistance in oesophageal cancer cells by activating glycolysis. Glycolysis levels increased in cisplatin-resistant ovarian cancer cells.

GLP-1RAs improve insulin sensitivity, reduce glucose variability, and lead to meaningful weight loss, which could indirectly create a less favourable environment for tumour progression in ovarian cancer patients, especially those with obesity or type 2 diabetes living in a hyperinsulinemic, pro-inflammatory state.

The human GIP gene encodes glucose-dependent insulinotropic polypeptide, a hormone primarily involved in glucose metabolism and insulin secretion from intestinal K-cells. There is no established scientific consensus or peer-reviewed evidence indicating that GIP functions as an oncogene specifically in ovarian tumors; research on oncogenes in ovarian cancer typically focuses on G-protein alpha subunits like GNA12/13 (gep oncogenes) or other GPCRs, but not the GIP hormone gene.