Significance Spontaneous overexpression of endogenous IRIS, an alternatively spliced product of the tumor suppressor gene BRCA1 , allows it to function as an oncoprotein that stimulates a potentially lethal outcome, i.e. metastasis of human cancer cells to tissues served, in part, by the arterial circulation. It does so by suppressing phosphatase and tensin homolog (PTEN) mRNA synthesis, thereby stabilizing and activating HIF-1α in normoxic cells. Thus, this study provides a strong rationale for exploring the therapeutic value of interfering with spontaneously overexpressed IRIS function in multiple types of tumors that can naturally overexpress it.