ERBB4 (HER4) is a member of the ERBB family of receptor tyrosine kinases, a family that includes the epidermal growth factor receptor (EGFR/ERBB1/HER1), ERBB2 (Neu/HER2), and ERBB3 (HER3). EGFR and ERBB2 are oncoproteins and validated targets for therapeutic intervention in a variety of solid tumors. In contrast, the role that ERBB4 plays in human malignancies is ambiguous. Thus, here we review the literature regarding ERBB4 function in human malignancies. We review the mechanisms of ERBB4 signaling with an emphasis on mechanisms of signaling specificity. In the context of this signaling specificity, we discuss the hypothesis that ERBB4 appears to function as a tumor suppressor protein and as an oncoprotein. Next, we review the literature that describes the role of ERBB4 in tumors of the bladder, liver, prostate, brain, colon, stomach, lung, bone, ovary, thyroid, hematopoietic tissues, pancreas, breast, skin, head, and neck. Whenever possible, we discuss the possibility that ERBB4 mutants function as biomarkers in these tumors. Finally, we discuss the potential roles of ERBB4 mutants in the staging of human tumors and how ERBB4 function may dictate the treatment of human tumors.

中文翻译：

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ERBB4的阴阳：肿瘤抑制因子和癌蛋白

ERBB4 (HER4) 是受体酪氨酸激酶 ERBB 家族的成员，该家族包括表皮生长因子受体 (EGFR/ERBB1/HER1)、ERBB2 (Neu/HER2) 和 ERBB3 (HER3)。EGFR 和 ERBB2 是癌蛋白，也是多种实体瘤治疗干预的经过验证的靶点。相比之下，ERBB4 在人类恶性肿瘤中发挥的作用则不明确。因此，我们在此回顾有关 ERBB4 在人类恶性肿瘤中的功能的文献。我们回顾了 ERBB4 信号传导机制，重点是信号传导特异性机制。在这种信号传导特异性的背景下，我们讨论了 ERBB4 似乎充当肿瘤抑制蛋白和癌蛋白的假设。接下来，我们回顾了描述 ERBB4 在膀胱、肝脏、前列腺、脑、结肠、胃、肺、骨、卵巢、甲状腺、造血组织、胰腺、乳房、皮肤、头部和颈部肿瘤中作用的文献。只要有可能，我们就会讨论 ERBB4 突变体作为这些肿瘤生物标志物的可能性。最后，我们讨论了 ERBB4 突变体在人类肿瘤分期中的潜在作用，以及 ERBB4 功能如何决定人类肿瘤的治疗。