Hemodynamic shear stress induces protective autophagy in HeLa cells through lipid raft-mediated mechanotransduction
Hemodynamic shear stress induces protective autophagy in HeLa cells through lipid raft-mediated mechanotransduction
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DOI：
10.1007/s10585-018-9887-9
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发表时间：
2018-03-01
影响因子：
4
通讯作者：
Maiti, Tapas K.
中科院分区：
文献类型：
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作者：
Das, Joyjyoti;Maji, Somnath;Maiti, Tapas K.
在转移性播散期间，癌细胞在体内脉管系统的狭窄限制中经历剪切应力。目前已知这种压力影响细胞过程的范围。虽然来自原发性肿瘤的大量细胞由于剪切而在循环中死亡，但一些细胞设法迁移到远处的小生境并形成继发性肿瘤。目前的研究重点是癌细胞如何避免这种机械应力并适应自己以生存。本研究探讨了宫颈癌细胞HeLa及其亚系HeLa 229在体外生理剪切应力下的自噬反应，并评估了其作为促生存机制的作用。它还描绘了可能的机械转导途径，参与引发宫颈癌细胞的应激适应性反应。我们的研究结果表明，生理机制的剪切应力在宫颈癌细胞中激发保护性自噬作为一种即时反应，并抑制自噬，导致细胞凋亡的早期发生。研究潜在的机械转导的努力表明，自噬诱导的剪切应力需要完整的脂筏作为信号平台，以触发磷酸化的p38丝裂原活化蛋白激酶，导致自噬。因此，这项研究为宫颈癌的机械生物学提供了新的见解，并暗示了转移的有希望的治疗靶点，转移是癌症死亡的主要原因。
During metastatic dissemination, cancer cells experience shear stresses in narrow confinements of in vivo vasculature. Such stresses are currently known to influence a gamut of cellular processes. While a host of cells emanating from a primary tumor perish in circulation due to shear, some cells manage to migrate to distant niches and form secondary tumors. Current research focuses on how cancer cells avert such mechanical stresses and adapt themselves in order to survive. This study deals with the autophagic response of cervical cancer cells HeLa and its subline HeLa 229, exposed to physiological shear stresses in vitro, and evaluates its role as a pro-survival mechanism. It also delineates the probable mechanotransduction pathway that is involved in eliciting the stress-adaptive response in cervical cancer cells. Our results show that shear stress of physiological regime elicits protective autophagy in cervical cancer cells as an immediate response and inhibiting the same, leads to early onset of apoptosis. An effort to study the underlying mechanotransduction revealed that autophagy induction by shear stress requires intact lipid rafts which serve as signalling platforms to trigger phosphorylation of p38 mitogen activated protein kinases, leading to autophagy. This study thus gives novel insights into the mechanobiology of cervical cancer and hints at promising therapeutic targets in metastasis, the major cause of cancer mortality.