Targeting INHBA in Ovarian Cancer Cells Suppresses Cancer Xenograft Growth by Attenuating Stromal Fibroblast Activation

Abstract

INHBA-encoded inhibin β A is a member of the transforming growth factor-β (TGF-β) superfamily. INHBA has been reported to be implicated in the progression of multiple types of cancer including ovarian cancer (OC). However, the mechanisms by which INHBA affects OC progression are not well-characterized. The aim of our study was to explore the prognostic value of INHBA for different stages and grades of OC and to identify the possible mechanisms by which INHBA promotes OC progression. Our results demonstrated that INHBA was specifically expressed in OC epithelium, and higher expression was associated with higher risk of mortality in patients with advanced and higher-grade serous OC (SOC). In addition, knockdown of INHBA in cancer cells impaired cancer xenograft growth through reducing OC stromal fibroblast activation in vivo. Further results confirmed that Smad2 signaling pathway was involved in INHBA-induced stromal fibroblast activation, and inhibiting this pathway could effectively reverse activation of stromal fibroblasts. In summary, our results showed that blocking INHBA in cancer cells may be a potential therapeutic strategy to inhibit SOC progression.

Inhibin β-A (INHBA) induces epithelial–mesenchymal transition and accelerates the motility of breast cancer cells by activating the TGF-β signaling pathway

“…A recent study showed that activin A overexpression promotes BC metastasis by activating Smad2 and inducing IL13Ra2 expression [10]. INHBA overexpression has been correlated with aggressive phenotype in different cancers, including colorectal cancer, lung adenocarcinoma, esophageal adenocarcinoma, ovarian cancer, and gastric cancer [11][12][13][14][15]. INHBA overexpression is also associated with a poor prognosis in gastric and lung cancer [14,16].…”

Prediction and identification of immune genes related to the prognosis of patients with colon adenocarcinoma and its mechanisms

“…There are also reports in the literature that the effect of suppressing the development of colon cancer can be achieved by immunosuppression of CXCL3 [23][24][25][26][27]. INHBA has a significant relationship with the occurrence and development of gastric, esophageal, and ovarian cancers, and studies have reported that the immunosuppressive treatment of INHBA can reduce the rate of deterioration of gastric and ovarian cancers [28][29][30]. STC1 can promote the metastasis of colon cancer [31,32].…”

Prediction and identification of immune genes related to the prognosis of patients with colon adenocarcinoma and its mechanisms

“…There are also reports in the literature that the effect of suppressing the development of colon cancer can be achieved by immunosuppression of CXCL3 [12][13][14][15][16]. INHBA has a significant relationship with the occurrence and development of gastric, esophageal, and ovarian cancers, and studies have reported that the immunosuppressive treatment of INHBA can reduce the rate of deterioration of gastric and ovarian cancers [17][18][19]. STC1OXTR, and UCN can promote the metastasis of colon cancer [20][21][22][23].…”