Ludueña Richard F, Walss-Bass Consuelo, Portyanko Anna, Guo Jiayan, Yeh I-Tien
Department of Biochemistry and Structural Biology, University of Texas Health Science Center at San Antonio, San Antonio, TX, United States.
Department of Psychiatry and Behavioral Sciences, University of Texas Health Science Center at Houston, Houston, TX, United States.
Front Cell Dev Biol. 2022 May 30;10:870088. doi: 10.3389/fcell.2022.870088. eCollection 2022.
Microtubules are organelles that usually occur only in the cytosol. Walss et al. (1999) discovered the βII isotype of tubulin, complexed with , in the nuclei of certain cultured cells, in non-microtubule form. When fluorescently labeled tubulins were microinjected into the cells, only II appeared in the nucleus, and only after one cycle of nuclear disassembly and reassembly. It appeared as if II does not cross the nuclear envelope but is trapped in the nucleus by the re-forming nuclear envelope in whose reassembly II may be involved. II is present in the cytoplasm and nuclei of many tumor cells. With some exceptions, normal tissues that expressed βII rarely had βII in their nuclei. It is possible that βII is involved in nuclear reassembly and then disappears from the nucleus. Ruksha et al. (2019) observed that patients whose colon cancer cells in the invasive front showed no βII had a median survival of about 5.5 years, which was more than halved if they had cytosolic II and further lessened if they had nuclear II, suggesting that the presence and location of II in biopsies could be a useful prognostic indicator and also that II may be involved in cancer progression. Yeh and Ludueña. (2004) observed that many tumors were surrounded by non-cancerous cells exhibiting cytosolic and nuclear II, suggesting a signaling pathway that causes II to be synthesized in nearby cells and localized to their nuclei. II could be useful in cancer diagnosis, since the presence of II in non-cancerous cells could indicate a nearby tumor. Investigation of this pathway might reveal novel targets for chemotherapy. Another possibility would be to combine II with CRISPR-Cas9. This complex would likely enter the nucleus of a cancer cell and, if guided to the appropriate gene, might destroy the cancer cell or make it less aggressive; possible targets will be discussed here. The possibilities raised here about the utility of II in cancer diagnosis, prognosis, biology and therapy may repay further investigation.
微管是通常仅存在于细胞质溶胶中的细胞器。瓦尔兹等人（1999年）在某些培养细胞的细胞核中发现了与……复合的微管蛋白βII同种型，呈非微管形式。当将荧光标记的微管蛋白显微注射到细胞中时，只有βII出现在细胞核中，且仅在一轮核解体和重新组装之后。似乎βII不会穿过核膜，而是在重新组装的核膜（βII可能参与其重新组装）重新形成时被困在细胞核中。βII存在于许多肿瘤细胞的细胞质和细胞核中。除了一些例外情况，表达βII的正常组织在其细胞核中很少有βII。有可能βII参与核重新组装，然后从细胞核中消失。鲁克沙等人（2019年）观察到，侵袭前沿的结肠癌细胞中未显示βII的患者的中位生存期约为5.5年，如果他们的细胞质中有βII，中位生存期会减半以上，如果细胞核中有βII，中位生存期则会进一步缩短，这表明活检中βII的存在和位置可能是一个有用的预后指标，也表明βII可能参与癌症进展。叶和卢德尼亚（2004年）观察到，许多肿瘤被显示细胞质和细胞核中有βII的非癌细胞包围，这表明存在一种信号通路，导致附近细胞合成βII并将其定位到细胞核中。βII在癌症诊断中可能有用，因为非癌细胞中βII的存在可能表明附近有肿瘤。对这条通路的研究可能会揭示化疗的新靶点。另一种可能性是将βII与CRISPR-Cas9结合。这种复合物可能会进入癌细胞的细胞核，如果被引导至合适的基因，可能会破坏癌细胞或使其侵袭性降低；这里将讨论可能的靶点。这里提出的关于βII在癌症诊断、预后、生物学和治疗中的效用的可能性值得进一步研究。
