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Human epithelial ovarian cancer (EOC) is the fifth leading cause of cancer among women and has the highest mortality rate among gynaecological malignancies.The transforming growth factor-β (TGF-β) superfamily is a large group of growth factors that play important roles in many physiological and pathological processes, including cancer development.Members of the TGF-β superfamily signal through type Ⅰ and type Ⅱ serine/threonine kinase receptors and Smad proteins.Nodal, a member of TGF-β superfamily, is known to be a critical regulator of embryogenesis.Recently, we found that Nodal is expressed in EOC cell lines and tumor samples.We demonstrated that Nodal acts through activin receptor-like kinase 7 (ALK7) to inhibit proliferation and induce apoptosis in EOC cell lines.Interestingly, chemosensitive cells are more responsive to Nodal-ALK7 than their chemoresistant counterparts.Nodal activates Smad2/3 to induce the expression of proapoptotic factors, such as Bax, and to inhibit the expression of antiapoptotic factors, Bcl-2 and Xiap.Knockdown of Bax expression significantly blocked Nodal/ALK7-induced apoptosis.