Rodriguez Calleja Lidia, Lavaud Melanie, Tesfaye Robel, Brounais-Le-Royer Bénédicte, Baud'huin Marc, Georges Steven, Lamoureux François, Verrecchia Franck, Ory Benjamin
Nantes Université, CHILD Team, CRCI2NA, INSERM UMR 1307, CNRS UMR 6075, F-44000 Nantes, France.
Cancers (Basel). 2022 Dec 1;14(23):5948. doi: 10.3390/cancers14235948.
TP53 (TP53), p73 (TP73), and p63 (TP63) are members of the p53 transcription factor family, which has many activities spanning from embryonic development through to tumor suppression. The utilization of two promoters and alternative mRNA splicing has been shown to yield numerous isoforms in p53, p63, and p73. TAp73 is thought to mediate apoptosis as a result of nuclear accumulation following chemotherapy-induced DNA damage, according to a number of studies. Overexpression of the nuclear ΔNp63 and ΔNp73 isoforms, on the other hand, suppresses TAp73's pro-apoptotic activity in human malignancies, potentially leading to metastatic spread or inhibition. Another well-known pathway that has been associated to metastatic spread is the TGF pathway. TGFs are a family of structurally related polypeptide growth factors that regulate a variety of cellular functions including cell proliferation, lineage determination, differentiation, motility, adhesion, and cell death, making them significant players in development, homeostasis, and wound repair. Various studies have already identified several interactions between the p53 protein family and the TGFb pathway in the context of tumor growth and metastatic spread, beginning to shed light on this enigmatic intricacy.
TP53(TP53)、p73(TP73)和p63(TP63)是p53转录因子家族的成员,该家族具有许多活动,涵盖从胚胎发育到肿瘤抑制的过程。已证明利用两个启动子和可变mRNA剪接可在p53、p63和p73中产生众多异构体。根据多项研究,化疗诱导的DNA损伤后,TAp73被认为会因核积累而介导细胞凋亡。另一方面,核ΔNp63和ΔNp73异构体的过表达会抑制TAp73在人类恶性肿瘤中的促凋亡活性,这可能导致转移扩散或抑制。另一个与转移扩散相关的著名途径是TGF途径。TGF是一类结构相关的多肽生长因子家族,可调节多种细胞功能,包括细胞增殖、谱系确定、分化、运动、黏附及细胞死亡,使其成为发育、体内平衡和伤口修复中的重要参与者。在肿瘤生长和转移扩散的背景下,各种研究已经确定了p53蛋白家族与TGFb途径之间的几种相互作用,这开始揭示这种神秘的复杂性。