Yousaf Saba, Ahmad Muhammad, Wu Siwen, Zia Muhammad Anjum, Ahmed Ishtiaq, Iqbal Hafiz M N, Liu Qingyou, Rehman Saif Ur
State Key Laboratory for Conservation and Utilization of Subtropical Agro-Bioresources of Guangxi University, Nanning 530005, China.
Enzyme Biotechnology Laboratory, Department of Biochemistry, University of Agriculture Faisalabad, Faisalabad 38040, Pakistan.
Biomedicines. 2022 Nov 7;10(11):2833. doi: 10.3390/biomedicines10112833.
Cancers are worldwide health concerns, whether they are sporadic or hereditary. The fundamental mechanism that causes somatic or oncogenic mutations and ultimately aids cancer development is still unknown. However, mammalian cells with protein-only somatic inheritance may also contribute to cancerous malignancies. Emerging data from a recent study show that prion-like proteins and prions (PrP) are crucial entities that have a functional role in developing neurological disorders and cancer. Furthermore, excessive PrP expression profiling has also been detected in non-neuronal tissues, such as the lymphoid cells, kidney, GIT, lung, muscle, and mammary glands. PrP expression is strongly linked with the proliferation and metastasis of pancreatic, prostate, colorectal, and breast malignancies. Similarly, experimental investigation presented that the PrP expression, including the prion protein-coding gene (PRNP) and p53 ag are directly associated with tumorigenicity and metastasis (tumor suppressor gene). The ERK2 (extracellular signal-regulated kinase) pathway also confers a robust metastatic capability for PrP-induced epithelial to mesenchymal transition. Additionally, prions could alter the epigenetic regulation of genes and overactive the mitogen-activated protein kinase (MAPK) signaling pathway, which promotes the development of cancer in humans. Protein overexpression or suppression caused by a prion and prion-like proteins has also been linked to oncogenesis and metastasis. Meanwhile, additional studies have discovered resistance to therapeutic targets, highlighting the significance of protein expression levels as potential diagnostic indicators and therapeutic targets.
癌症是全球关注的健康问题，无论其是散发性还是遗传性的。导致体细胞或致癌突变并最终促进癌症发展的基本机制仍然未知。然而，具有仅蛋白质体细胞遗传的哺乳动物细胞也可能导致癌症恶性肿瘤。最近一项研究的新数据表明，朊病毒样蛋白和朊病毒（PrP）是在神经疾病和癌症发展中起功能性作用的关键实体。此外，在非神经组织如淋巴细胞、肾脏、胃肠道、肺、肌肉和乳腺中也检测到了过量的PrP表达谱。PrP表达与胰腺、前列腺、结肠和乳腺恶性肿瘤的增殖和转移密切相关。同样，实验研究表明，PrP表达，包括朊病毒蛋白编码基因（PRNP）和p53基因，与致瘤性和转移（肿瘤抑制基因）直接相关。ERK2（细胞外信号调节激酶）途径也赋予PrP诱导的上皮-间质转化强大的转移能力。此外，朊病毒可以改变基因的表观遗传调控并使丝裂原活化蛋白激酶（MAPK）信号通路过度活跃，从而促进人类癌症的发展。由朊病毒和朊病毒样蛋白引起的蛋白质过表达或抑制也与肿瘤发生和转移有关。同时，其他研究发现了对治疗靶点的抗性，突出了蛋白质表达水平作为潜在诊断指标和治疗靶点的重要性。
