Meniu
Asmeninė anketa Prisijungimas ir registracija
Atgal Pagrindinis » Autorių straipsniai » Medical Health » 2020 » Spalio » 19

How cancer cells escape crowded tumors

Cell nucleus deformation triggers a signaling cascade for cancer cell

Like people, cells in the human body protect their personal space. They seem to know how much space they need, and if it gets too tight, most cells prefer to break free. The mechanism enabling cells to evade crowded environments appears to involve an unusual player—the cell nucleus. This is what researchers from St. Anna Children's Cancer Research Institute Vienna, King's College London, Institute Curie Paris, and ETH Zürich in Basel showed in their recent work.

Tissue cells protect their 'personal space'

The human body consists of trillions of cells growing in confined volumes, which often leads to cell crowding. The crowding effect is exacerbated when cell growth and proliferation are out of control during tumor formation. This creates a compressive microenvironment for the constituent cells. How do tumor cells cope with the lack of space and compressive stresses? Answering this question, the investigators found that the cells are able to sense environmental compression.

To do so, they utilize their largest and stiffest internal compartment, the nucleus. Squeezing cells to the degree that physically deforms the nucleus causes the nuclear membranes to unfold and stretch. These changes are detected by specialized proteins, activating cellular contractility. The ability to develop contractile forces helps squeezing the cell out of its compressive microenvironment in an "evasion reflex" mechanism. Therefore, the study proposes that the nucleus operates as a ruler (see the accompanying illustration). It allows living cells to measure their personal space and trigger specific responses once the space becomes violated.

Fat restrictions to target metabolic vulnerability in cancer?

As the scientists describe in the paper, Ca2+-dependent phospholipase cPLA2 is a protein, which senses nuclear membrane stretch upon cell compression. The lead author Alexis Lomakin, Ph.D., emphasizes that cPLA2 represents a druggable target. "Pharmaceutical companies are currently testing small molecule inhibitors of cPLA2. Based on our data, downregulating the activity of cPLA2 in  might interfere with their ability to escape the primary tumor and metastasize to distant locations," explains Dr. Lomakin.

cPLA2-inhibitors prevent the production of arachidonic acid (ARA), which subsequently affects cell migration, growth, and survival. However, ARA can also be obtained by cells from their environment. The Western diet, for instance, is a potent source of omega-6 fatty acids, such as ARA. Dietary fat restriction and consumption of omega-3 instead of omega-6  could synergize with cPLA2 inhibitors to effectively attenuate tumor cell escape from overcrowded areas. "Testing these hypotheses is an exciting direction for future research," concludes Dr. Lomakin.

Dr. Lomakin talsk abaout his publication in Science: "The nucleus acts as a ruler tailoring cell responses to spatial constraints. Credit: St. Anna Children´s Cancer Research Institute

Potential predictive marker for chemo-resistance

Identifying the cell nucleus as an active player that rapidly converts mechanical inputs into signaling or metabolic outputs is surprising. Until today, the nucleus was considered as a passive storehouse for genetic material. "We are very excited about what comes next," says Dr. Lomakin. According to him, high degrees of nuclear deformation could be predictive of metastatic potential and resistance to chemotherapy and immunotherapy.

"For many years, pathologists have been evaluating changes in the shape of the nucleus to discriminate between different stages of tumor growth; however, how these structural-mechanical alterations of the nucleus functionally impact cancer remained completely unexplored," says Dr. Lomakin.

  • by St. Anna Children's Cancer Research Institute
  • Cell nucleus deformation triggers a signaling cascade for cancer cell escape. Credit: Wojciech Garncarz (St. Anna Children's Cancer Research Institute)
Pasaulio naujienas kitaip... skaitykite Paranormal Telegram, FB ir X(twitter) kanale

...kadangi jau perskaitėte šį straipsnį iki pabaigos, prašome Jus prisidėti prie šio darbo. Skaitykite „Paranormal.lt“ ir toliau, skirdami kad ir nedidelę paramos sumą. Paremti galite Paypal arba SMS. Kaip tai padaryti? Iš anksto dėkojame už paramą! Nepamirškite pasidalinti patikusiais tekstais su savo draugais ir pažįstamais.

Turite savo nuomone, tapk autoriumi, prisijunk ir rašykite bloge. Dalinkitės receptais, sveikatos patarimais, nutikimais, susidūrėte su nekasdieniškais reiškiniais. Galite išversti iš užsienio kalbos, talpinkite su nuoroda. Laukiame Jūsų straipsnių, naujienų, apžvalgų ar istorijų!

Niekas neišdrįso palikti komentaro.
Būkite pirmi, kurie pasidalins savo nuomonėmis su kitais.
avatar

Nemokami skelbimai

TAIP PAT SKAITYKITE:
26.03.2024 laikas 11:01 Receptai – Patiekalai Jautienos liežuvis su krienų ir majonezo padažu
Besiartinant šventėmis vis dažniau sugrįžtu į lietuvišką virtuvę. Prisiminimai apie Kalėdas padeda prisiminti tai ką gamindavo šioms šventėms mano mama, ką gaminau prieš keletą metų pati. Yra patiekalų kurie ruošiami ne taip ir da...

Skaityti daugiau

25.03.2024 laikas 16:56 Receptai – Patiekalai "Sugaišau 10 minučių, o svečiai liko sužavėti": obuolių desertas arbatai (greitai ir nebrangiai)
Paruošti šį desertą man prireikė tiesiog 10 minučių, o mano svečiai manė, kad tam sugaišau pusę dienos! Nuostabus obuolių desertas, pagamintas iš pačių pigiausių produktų. Labai rekomenduoju visiems jį išbandyti! Dalinuosi receptu...

Skaityti daugiau

22.03.2024 laikas 21:32 Receptai – Patiekalai Stulbinamai skanūs sausainiai su įdaru (nebrangus receptas)
Dievinu naminį kepimą ir dažnai eksperimentuoju virtuvėje! Šiandien siūlau pasigaminti minkštų, skanių ir gražių sausainių.

Skaityti daugiau

28.03.2024 laikas 22:20 Finansinis horoskopas visiems Zodiako ženklams 2024 m. kovo 29 d.
Siūlome jums trumpą horoskopą 2024 m. kovo 29 d., penktadieniui, kuris padės kiekvienam Zodiako ženklo atstovui šią dieną būti budriam ir atsargiam.

Skaityti daugiau

28.03.2024 laikas 20:55 Sąnariams padės citrina ir jodas
Įvairių ligų gydymui aš dažnai naudoju liaudiškus receptus. Jums pateikiu tuos, kurie padėjo man pačiai.

Skaityti daugiau

28.03.2024 laikas 20:09 Kokie vaistiniai augalai palengvina gripo pasekmes?

Šaltyje atsirandantis, o šilumoje pranykstantis kosulys gali pažymėti refleksinę organizmo reakciją į šaltį, aštrius kvapus, dūmus, dulkes. Staiga kosėti žmogus dažnai pradeda, kai suserga virusine infekcija. Tokiu atveju būtina nustatyti kosulį s...

Skaityti daugiau